Publications (20)77 Total impact
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Article: Melatonin and hypothalamic-pituitary-gonadal axis.
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ABSTRACT: Melatonin (N-acetyl-5-methoxy-tryptamine), a principal product of the pineal gland, is produced mainly during the dark phase of the circadian cycle. This hormone plays a crucial role in the regulation of circadian and seasonal changes in various aspects of physiology and neuroendocrine functions. In mammals, melatonin can influence sexual maturation and reproductive functions via activation of its receptors and binding sites in the hypothalamic-pituitary-gonadal (HPG) axis. This review summarizes current knowledge of melatonin on the hypothalamus, pituitary gland, and gonads. We also review recent progress in clinical applications of melatonin or potentials of using melatonin, as a reducer of oxidative stress, to improve reproductive functions for the diseases such as women infertility.Current Medicinal Chemistry 02/2013; · 4.86 Impact Factor -
Article: Aerobic exercise increases BKCa channel contribution to regulation of mesenteric arterial tone by up regulating β1-Subunit.
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ABSTRACT: Substantial evidence has shown that exercise training produces numerous adaptations within the arteries. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels are expressed broadly on smooth muscle cells (SMCs) and play an important role in the regulation of vascular tone. The present study was designed to investigate the mechanisms of BKCa channel underlying the exercise-induced improvement of the vascular function in mesenteric arteries (MA). Male Wistar rats (180-200g) were trained for 12 weeks on a treadmill, and compared with age-matched sedentary animals (SED). Blood pressure and vascular contractility of MA were measured. Inside-out patch-clamp recording was applied on the freshly separated mesenteric SMCs to investigate the gating characteristics of BKCa channels. Western immunoblotting was performed to study expression levels of BKCa channel proteins. The maximal vascular contraction induced by NE (3×10(-5)M) was decreased after exercise training. TEA (3×10(-3)M) and Iberiotoxin (3×10(-8)M) induced a significant increase of vessel tension in both SED and EX (exercise training) groups, but these effects were more pronounced in EX rats compared with SED animals. Inside-out patch clamp recording showed that exercise training significantly increased the open probability, decreased the mean closed time and increased the mean open time, and the sensitivity to Ca(2+) and voltage without altering the unitary conductance. The expression of BK(Ca) β1- but not α- subunit was significantly enhanced after exercise training. These data suggest that exercise training increases the contribution of BK(Ca) channel to regulation of vascular tone in MA, which is possibly mediated by upregulating β1-subunit protein to increase BK(Ca) channel activity.Experimental physiology 06/2012; · 3.17 Impact Factor -
Article: Effect of exercise training volume on arterial contractility and BK(Ca) channel activity in rat thoracic aorta smooth muscle cells.
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ABSTRACT: Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels play a critical role in regulating cellular excitability and vascular tone. Exercise training showed reversible beneficial effects on cardiovascular systems with an improvement of vascular functions. This study investigated the effects of exercise training volume on vascular function and BK(Ca) channel activity in thoracic aorta smooth muscle cells (SMCs) in 20 sedentary (SED) and 40 training rats, submitted to a treadmill training protocol (20 m/min, 60 min/day, 12 weeks). Training rats were divided into two groups, exercising 3 days/week (EX1) and 5 days/week (EX2). Since intensity and duration of exercise were identical between training groups, the training volume was higher in EX2 than in EX1. Exercise training not only decreased heart rate, but also attenuated pressor responses induced by angiotensin II or norepinephrine (NE). The maximal vascular contraction induced by 10(-5) M NE was significantly decreased after training. In precontracted thoracic aorta with NE (10(-5) M), activation of the BK(Ca) channels by NS1619 significantly decreased the tension. The sensitivity of tissue to NS619 (pD2) was significantly correlated with volume of training (SED < EX1 < EX2). Inside-out patch clamp recording on aortic SMCs showed that exercise training significantly increased the open probability, decreased the mean closed time and increased the mean open time of BK(Ca) channels. This effect was more significant in the EX2 group than in the EX1 group. These data suggest that there is a dose effect for exercise training volume for the activation of BK(Ca) channels in vascular SMCs, which contributes to improvement of the arterial function in thoracic aortas.Arbeitsphysiologie 02/2012; 112(10):3667-78. · 2.15 Impact Factor -
Article: Central angiotensin I increases swallowing activity and oxytocin release in the near-term ovine fetus.
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ABSTRACT: The brain renin-angiotensin system (RAS) plays an important role in hydromineral and neuroendocrine balance. Although previous studies showed that exogenous angiotensin (Ang) II increased dipsogenic and vasopressin responses in near-term fetuses, little is known about the functional development of fetal endogenous brain RAS in the regulation of body fluid homeostasis. To determine the functional development of the central angiotensin-converting enzyme (ACE) in utero, we investigated the electrocortical (ECoG) activity, swallowing activity, oxytocin (OT) release, and c-fos expression in response to intracerebroventricular Ang I administration in the near-term fetal lamb. Ang I did not change fetal low-voltage (LV) and high-voltage (HV) ECoG temporal distributions, but increased fetal swallowing activity during LV ECoG (1.0±0.1 to 3.5±0.4 swallows/min). Additionally, Ang I evoked an increase in c-fos-immunoreactivity in putative dipsogenic centers, including the supraoptic and paraventricular nuclei of the hypothalamus, accompanied by an increase in fetal plasma OT levels. The expression of c-fos was demonstrated in OT neurons in the hypothalamus. The Ang I-mediated increase in fetal swallowing and plasma OT was inhibited by captopril. These results demonstrate the functional development of the fetal brain ACE system in the last trimester of gestation, which plays an important role in the RAS-mediated dipsogenic response and OT release in the regulation of body fluid homeostasis.Neuroendocrinology 11/2011; 95(3):248-56. · 2.38 Impact Factor -
Article: Central angiotensin I increases fetal AVP neuron activity and pressor responses.
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ABSTRACT: Angiotensin (Ang) II plays a critical role in cardiovascular homeostasis and neuroendocrine regulation. Little is known about whether central angiotensin-converting enzyme (ACE) is functional in the fetal brain. We investigated cardiovascular and neuroendocrinological responses to intracerebroventricular (icv) application of Ang I in the chronically prepared near-term ovine fetus in utero and examined the action sites marked by c-fos expression in the fetal hypothalamus. ACE mRNA was detected in the specific central areas. Intracerebroventricular Ang I significantly increased fetal blood pressure and c-fos expression in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) in the hypothalamus, accompanied by an increase of fetal plasma arginine vasopressin (AVP). Double labeling demonstrated that AVP neurons in the fetal SON and PVN were expressing c-fos. Captopril, an inhibitor of ACE, significantly suppressed fetal pressor responses and plasma AVP. Double labeling experiments showed colocalization of AT(1) receptor (AT(1)R) and c-fos expression in both SON and PVN following icv Ang I. The results indicate that central endogenous ACE has been functional at least at the last third of gestation and the endogenous brain renin-angiotensin system-mediated pressor responses and AVP release via AT(1)Rs by acting at the sites consistent with the cardiovascular network in the hypothalamus.AJP Endocrinology and Metabolism 04/2010; 298(6):E1274-82. · 4.75 Impact Factor -
Article: Angiotensin-converting enzymes and drug discovery in cardiovascular diseases.
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ABSTRACT: Angiotensin-converting enzyme (ACE) is a major target in the treatment of cardiovascular diseases (CVDs). In addition to ACE, ACE2 - which is a homolog of ACE and promotes the degradation of angiotensin II (Ang II) to Ang (1-7) - has been recognized recently as a potential therapeutic target in the management of CVDs. This article reviews different metabolic pathways of ACE and ACE2 (Ang I-Ang II-AT1 receptors and Ang I-Ang (1-7)-Mas receptors) in the regulation of cardiovascular function and their potential in new drug development in the therapy of CVDs. In addition, recent progress in the study of angiotensin and ACE in fetal origins of CVD, which might present an interesting field in perinatal medicine and preventive medicine, is briefly summarized.Drug discovery today 02/2010; 15(9-10):332-41. · 6.63 Impact Factor -
Article: Maturation and the role of PKC-mediated contractility in ovine cerebral arteries.
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ABSTRACT: Ca2+-independent pathways such as protein kinase C (PKC), extracellular-regulated kinases 1 and 2 (ERK1/2), and Rho kinase 1 and 2 (ROCK1/2) play important roles in modulating cerebral vascular tone. Because the roles of these kinases vary with maturational age, we tested the hypothesis that PKC differentially regulates the Ca2+-independent pathways and their effects on cerebral arterial contractility with development. We simultaneously examined the responses of arterial tension and intracellular Ca2+ concentration and used Western immunoblot analysis to measure ERK1/2, RhoA, 20 kDa regulatory myosin light chain (MLC20), PKC-potentiated inhibitory protein of 17 kDa (CPI-17), and caldesmon. Phorbol 12,13-dibutyrate (PDBu)-mediated PKC activation produced a robust contractile response, which was increased a further 20 to 30% by U-0126 (MEK inhibitor) in cerebral arteries of both age groups. Of interest, in the fetal cerebral arteries, PDBu leads to an increased phosphorylation of ERK2 compared with ERK1, whereas in adult arteries, we observed an increased phosphorylation of ERK1 compared with ERK2. Also, in the present study, RhoA/ROCK played a significant role in the PDBu-mediated contractility of fetal cerebral arteries, whereas in adult cerebral arteries, CPI-17 and caldesmon had a significantly greater role compared with the fetus. PDBu also led to an increased MLC20 phosphorylation, a response blunted by the inhibition of myosin light chain kinase only in the fetus. Overall, the present study demonstrates an important maturational shift from RhoA/ROCK-mediated to CPI-17/caldesmon-mediated PKC-induced contractile response in ovine cerebral arteries.AJP Heart and Circulatory Physiology 09/2009; 297(6):H2242-52. · 3.71 Impact Factor -
Article: Development of fetal brain renin-angiotensin system and hypertension programmed in fetal origins.
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ABSTRACT: Since the concept of fetal origins of adult diseases was introduced in 1980s, the development of the renin-angiotensin system (RAS) in normal and abnormal patterns has attracted attention. Recent studies have shown the importance of the fetal RAS in both prenatal and postnatal development. This review focuses on the functional development of the fetal brain RAS, and ontogeny of local brain RAS components in utero. The central RAS plays an important role in the control of fetal cardiovascular responses, body fluid balance, and neuroendocrine regulation. Recent progress has been made in demonstrating that altered fetal RAS development as a consequence of environmental insults may impact on "programming" of hypertension later in life. Given that the central RAS is of equal importance to the peripheral RAS in cardiovascular regulation, studies on the fetal brain RAS development in normal and abnormal patterns could shed light on "programming" mechanisms of adult cardiovascular diseases in fetal origins.Progress in Neurobiology 05/2009; 87(4):252-63. · 8.87 Impact Factor -
Article: A new approach for exploring functional development of fetal brain pathways.
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ABSTRACT: Study of functional development of central pathways in fetuses is challenging due to the lack of methods available. In this article, we present a novel approach to test if and when central functional pathways are established by a combination of mapping with c-fos and chronically cannulated fetuses in utero. This approach is based on brain structures such as circumventricular organs (CVOs) that lack the blood-brain barrier (BBB), but are rich in sensors to peripheral signals and contain projections to other brain regions. If signaling molecules in the blood that are too large to cross the BBB induced c-fos expression in both the CVOs and other nuclei inside the fetal brain, this can be evidence that projections from the CVOs to those nuclei are established and functional. This is a useful real-time method to explore the status of functional maturation of pathways between the CVOs and other brain areas in developing fetuses. Notably, at the moment, this is the first and only in vivo method that can detect functional projections in the fetal brain in vitro.Developmental Psychobiology 04/2009; 51(4):384-8. · 2.98 Impact Factor -
Article: Central cholinergic mechanisms mediate swallowing, renal excretion, and c-fos expression in the ovine fetus near term.
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ABSTRACT: Fetal swallowing and renal metabolism contribute importantly to amniotic and body fluid homeostasis. To determine central cholinergic modulation of swallowing activity and renal excretion associated with neural activity, we examined the effects of intracerebroventricular injection of carbachol, a cholinergic agonist, in ovine fetuses at 0.9 gestation. Fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram electrodes, as well as lateral ventricle and vascular catheters. Electrodes were also implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, and urine output were monitored during basal period and the experimental period following intracerebroventricular injection of 0.9% NaCl as the control (n = 5) or carbachol (3 microg/kg, n = 5). Central carbachol did not significantly change fetal low voltage (LV) and high voltage (HV) ECoG temporal distributions. However, swallowing activity during LV ECoG was elevated significantly after intracerebroventricular carbachol. Associated with the swallowing activation, c-fos immunoreactivity in the putative dipsogenic center, subfornical organ, was enhanced significantly. The fetal urine flow rate and renal Na+, K+, and Cl(-) excretion were markedly increased following intracerebroventricular carbachol and sustained at the high level for at least 2 h. The results indicate that the central cholinergic mechanism is established and functional in regulation of fetal behavior and renal excretion at least at 0.9 gestation, which plays an important role in maintenance of fetal body fluid homeostasis.AJP Regulatory Integrative and Comparative Physiology 12/2008; 296(2):R318-25. · 3.34 Impact Factor -
Article: Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and oxytocin in ovine fetuses.
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ABSTRACT: The hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. It is well established that central cholinergic mechanisms are critical in the regulation of cardiovascular responses and maintenance of body fluid homeostasis in adults. Our recent study demonstrated that intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of blood pressure in the near-term ovine fetuses. However, in utero development of brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides is largely unknown. This study investigated AVP and OT neural activation in the fetal hypothalamus induced by central carbachol. Chronically prepared near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3 microg/kg). Fetal blood samples were collected for AVP and OT assay, and brains were used for c-fos mapping studies. I.c.v. carbachol significantly increased fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in the hypothalamus. Double labeling demonstrated that a number of AVP- and OT-containing neurons in the fetal SON and PVN were expressing c-fos in response to central carbachol. The results indicate that the central cholinergic mechanism is established and functional in the regulation of the hypothalamic neuropeptides during the final trimester of pregnancy. This provides evidence for a functional link between the development of central cholinergic mechanisms and hypothalamic neuropeptide systems in the fetus.BMC Developmental Biology 11/2008; 8:95. · 2.79 Impact Factor -
Article: Effects of i.c.v. losartan on the angiotensin II-mediated vasopressin release and hypothalamic fos expression in near-term ovine fetuses.
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ABSTRACT: Our previous studies have shown that central administration of angiotensin (ANG II) causes arginine vasopressin (AVP) release in the fetus at 70-90% gestation. This is evidence that the hypothalamic-neurohypophysial system is relatively mature before birth. However, few data exist regarding central ANG receptor mechanisms-mediated AVP response during fetal life. To determine roles of brain ANG receptor subtypes in this response, AT1 and AT2 receptor antagonists, losartan and PD123319, were investigated in the brain in chronically prepared ovine fetuses at the last third of gestation. Application of losartan intracerebroventricularly (i.c.v.) at 0.5 mg/kg suppressed central ANG II-stimulated plasma AVP release. Losartan at 5 mg/kg (i.c.v.) demonstrated a significant enhancement of AVP increase to i.c.v. ANG II. Associated with the increase of plasma vasopressin levels, c-fos expression in the hypothalamic neurons was significantly different between the low and high doses of losartan. The low dose losartan markedly reduced the dual immunoreactivity for FOS and AVP in the supraoptic nuclei and paraventricular nuclei after i.c.v. ANG II, whereas the high dose losartan together with ANG II, significantly increased the co-localization of positive FOS in the AVP-containing neurons than that induced by i.c.v. ANG II alone. Central ANG II induced fetal plasma vasopressin increase was not altered by PD123319. The data suggest that losartan in the fetal brain has remarkably different effects based on the doses administrated on central ANG II-related neuroendocrine effects at the late gestation, and that the AT1 mechanism is critical in the regulation of fetal body fluid homeostasis related to plasma AVP levels.Peptides 10/2006; 27(9):2230-8. · 2.43 Impact Factor -
Article: The association of cardiovascular responses with brain c-fos expression after central carbachol in the near-term ovine fetus.
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ABSTRACT: Central cholinergic mechanisms play important roles in the control of cardiovascular responses. However, in utero development of brain cholinergic mechanism in regulation of arterial pressure before birth is largely unknown. This study investigated cardiovascular responses to central application of carbachol in fetuses and determined functional development of the central cholinergic systems controlling fetal pressor responses in utero. Chronically prepared near-term ovine fetuses (90% gestation) received an injection of carbachol intracerebroventricularly (i.c.v.). Fetal cardiovascular responses were measured, and the brains were used for c-fos mapping studies. In response to carbachol injection i.c.v., fetal systolic, diastolic, and mean arterial pressure (MAP) immediately increased, accompanied by a bradycardia. The maximum increase of MAP was at 30 min after the i.c.v. injection of carbachol and lasted 90 min. Associated with the pressor response, the neuronal activity marked with c-fos was enhanced significantly in the fetal anterior third ventricle (AV3V) region (including the median preoptic nucleus and organum vasculosum of the lamina terminalis) in the forebrain, and in the area postrema, lateral parabrachial nucleus, nucleus tractus solitary, and rostral ventrolateral medulla in the hindbrain. These results indicate that the central cholinergic mechanism is functional in the control of fetal blood pressure at the last third of gestation, and the central AV3V region and hindbrain have been intact relatively during in utero development in sheep at 90% gestational stage.Neuropsychopharmacology 01/2006; 30(12):2162-8. · 7.99 Impact Factor -
Article: Effects of intracerebroventricular losartan on angiotensin II-mediated pressor responses and c-fos expression in near-term ovine fetus.
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ABSTRACT: The renin-angiotensin system plays an important role in cardiovascular control. Intracerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor response in the fetus at 90% gestation. To determine the roles of brain AT1 and AT2 receptors in this response, the effects of the central AT1 and AT2 receptor antagonists losartan and PD123319 were investigated in chronically prepared near-term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG II-induced pressor responses. High-dose losartan (5 mg/kg, i.c.v.) showed a potentiation of the pressor response to i.c.v. ANG II, accompanied by bradycardia. Associated with the pressor responses, c-fos expression in the cardiovascular controlling areas was significantly different between the low and high doses of losartan. These areas included the subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis, and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, lateral parabrachial nuclei in the hindbrain. Low-dose losartan markedly reduced c-fos in these areas after i.c.v. ANG II, while the high-dose losartan together with ANG II elicited a much stronger FOS-immunoreactivity in these areas than that induced by i.c.v. ANG II alone. This is a novel finding, that c-fos expression in the brain can be both activated and inhibited under the same condition. Central ANG II-induced fetal pressor responses were not altered by PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a low dose has strikingly different effects on central ANG II-induced pressor responses in fetuses at late gestation, and that the AT1 mechanism plays an important role in fetal cardiovascular regulation.The Journal of Comparative Neurology 01/2006; 493(4):571-9. · 3.81 Impact Factor -
Article: Angiotensin-induced vasopressin release and activation of hypothalamic neuron in pre-term fetuses.
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ABSTRACT: Our previous studies have shown that central administration of angiotensin II (ANG II) causes vasopressin release in the near-term fetus in utero as evidence that the hypothalamic-neurohypophysial system has relatively matured before birth. However, it is still unknown whether the vasopressin controlling centers have been functionally developed in younger fetuses. This study determined fetal plasma vasopressin levels and hypothalamic vasopressin neuron activity in the chronically instrumented pre-term ovine fetuses. Introcerebroventricular (i.c.v.) administration of ANG II did not affect fetal plasma osmolality and sodium concentrations. However, fetal plasma vasopressin levels were significantly increased ( approximately 3-fold) in response to central injection of ANG II. Central ANG II also induced vasopressin-neuron activity marked with c-fos expression in the fetal hypothalamus at pre-term. In addition, the fetal organum vasculosum of the lamina terminalis and the subfornical organ were activated. The results suggest that hypothalamic-neurohypophysial system has been relatively intact and functional at 70% gestational age, and that central angiotensin is important in inducing fetal vasopressin release in utero.Peptides 03/2005; 26(2):307-14. · 2.43 Impact Factor -
Article: Vasopressin mechanism-mediated pressor responses caused by central angiotensin II in the ovine fetus.
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ABSTRACT: AVP not only influences renal water excretion but also has profound cardiovascular effects in adults. Our recent studies have demonstrated that central angiotensin induced fetal pressor responses accompanied with AVP release. However, little is known of hormonal mechanisms in angiotensin-mediated fetal blood pressure (BP) changes. The present study determined AVP mechanisms in central angiotensin-mediated fetal pressor responses. The V1-receptor antagonist or V2-receptor antagonist was infused intravenously into the ovine fetus at 90% gestation. Angiotensin II (Ang II; 1.5 microg/kg) was then injected intracerebroventricularly into the chronically instrumented fetus. Ang II produced a significant increase in fetal systolic, diastolic, and mean arterial pressure adjusted to amniotic pressure (A-MAP). The enhanced fetal A-MAP was associated with intense c-fos expression in the central putative cardiovascular area: the paraventricular nuclei (PVN). Double labeling demonstrated that a number of the AVP-containing neurons in the PVN were expressing c-fos in response to central Ang II. Consistent with the activation of AVP neurons in the PVN, fetal plasma AVP was markedly enhanced. Fetal i.v. V1-receptor antagonist or V2-receptor antagonist had no effect on either fetal or maternal baseline BP. However, intracerebroventricular Ang II-increased BP was partially inhibited, although not completely abolished, by the V1-receptor blockade. In contrast, fetal i.v. infusion of V2-receptor antagonist had no effect on the pressor responses induced by central Ang II. The results suggest that the central Ang II-mediated pressor responses at the last third of gestation is mediated partially by the AVP mechanism via V1 not V2 receptors.Pediatric Research 12/2004; 56(5):756-62. · 2.70 Impact Factor -
Article: Induced fetal depressor or pressor responses associated with c-fos by intravenous or intracerebroventricular losartan.
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ABSTRACT: Previous fetal studies have indicated depressor responses of intravenous (i.v.) administration of angiotensin antagonists. However, little is known of central effects of angiotensin blockers on fetal cardiovascular controlling. The cardiovascular effects of central administration of the angiotensin-1 (AT(1)) and angiotensin-2 (AT(2)) receptor antagonists, losartan and PD123319, were investigated in the chronically catheterized near-term ovine fetuses. Intravenous losartan produced within 1.5 min a significant and persistent depressor response [maximum Delta mean arterial pressure (MAP)=9 mm Hg] without altering fetal heart rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5 mg/kg) increased fetal arterial pressures (Delta MAP=9-14 mm Hg). Central application of losartan (1 mg/kg) also increased fetal heart rate (maximum Delta heart rate=33 beat per minute). Losartan increased c-fos expression in the median preoptic nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain. These brain sectors are with abundant AT(1) receptors and have been demonstrated in the involvement in cardiovascular regulation. In contrast, intracerebroventricular injection of the AT(2) receptor antagonist PD123319 had no effect on fetal arterial pressure and heart rate. The results demonstrate strikingly functional differences of losartan on the fetal cardiovascular regulation in central and peripheral sides.Developmental Brain Research 11/2004; 153(1):53-60. · 1.78 Impact Factor -
Article: Central angiotensin II-induced pressor responses and neural activity in utero and hypothalamic angiotensin receptors in preterm ovine fetus.
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ABSTRACT: The central renin-angiotensin system is important in the control of blood pressure in the adult. However, few data exist about the in utero development of central angiotensin-mediated pressor responses. Our recent studies have shown that the application of ANG II into the fetal brain can increase blood pressure at near term. The present study determined fetal blood pressure and heart rate in response to a central application of ANG II in the chronically prepared preterm ovine fetus, determined the action sites marked by c-Fos expression in the fetal central pathways after intracerebroventricular injection of ANG II in utero, and determined angiotensin subtype 1 receptors in the fetal hypothalamus. Central injection of ANG II significantly increased fetal mean arterial pressure (MAP). Adjusted fetal MAP against amniotic pressure was also increased by ANG II. Fetal heart rate was subsequently decreased after the central administration of ANG II and/or the increase of blood pressure. ANG II induced c-Fos expression in the central putative cardiovascular area, the paraventricular nuclei in the brain sympathetic pathway. Application of ANG II also caused intense Fos immunoreactivity in the tractus solitarius nuclei in the hindbrain. In addition, intense angiotensin subtype 1 receptors were expressed in the hypothalamus at preterm. These data demonstrate that central ANG II-related pressor centers start to function as early as at preterm and suggest that the central angiotensin-related sympathetic pathway is likely intact in the control of blood pressure in utero.AJP Heart and Circulatory Physiology 05/2004; 286(4):H1507-14. · 3.71 Impact Factor -
Article: Intravenous angiotensin induces brain c-fos expression and vasopressin release in the near-term ovine fetus.
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ABSTRACT: The effect of intravenous angiotensin II (ANG II) on fetal brain c-fos expression and arginine vasopressin (AVP) release was studied in the near-term ovine fetus. Fetuses with chronically implanted catheters received an intravenous infusion of ANG II or saline. Fetal plasma AVP concentrations were significantly increased after the peripheral administration of ANG II, with peak levels (3-fold) at 30 min after the intravenous infusion. There was no change in fetal plasma osmolality, sodium, and hematocrit levels between the control and experimental groups or between the periods before and after the infusion of ANG II. Intravenous ANG II administration induced Fos immunoreactivity (Fos-IR) in the circumventricular organs and the median preoptic nucleus of the fetal brain. Fos-IR was also demonstrated in the fetal supraoptic nuclei (SON). Double labeling demonstrated that the AVP-containing neurons in the SON were expressing c-fos in response to intravenous ANG II. These results indicate that the peripheral ANG II in the fetus may play a significant role in stimulating the central hypothalamic-neurohypophysial system during late gestation. It supports the hypothesis that circulating ANG II may act at the fetal AVP neurons in the hypothalamus in body fluid balance via the circumventricular organs, which are situated outside the blood-brain barrier, and the central neural pathway between these two brain structures has been relatively established in utero, at least at near-term.AJP Endocrinology and Metabolism 01/2004; 285(6):E1216-22. · 4.75 Impact Factor -
Article: In utero development of central ANG-stimulated pressor response and hypothalamic fos expression.
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ABSTRACT: Central renin-angiotensin system (RAS) is as important as the peripheral RAS in the control of the cardiovascular homeostasis in the adult. However, previous fetal studies on angiotensin II (ANG II)-induced cardiovascular responses focused exclusively on the peripheral side. Thus, few data exist characterizing the in utero development of central angiotensin-mediated pressor responses. The present study determined cardiovascular responses to central application of ANG II in the chronically prepared near-term ovine fetus, and determined the action sites marked by c-fos expression in the fetal hypothalamus following intracerebroventricular (icv) injection of ANG II in utero. ANG II significantly increased fetal systolic, diastolic, and mean arterial pressure (MAP) within 5 min after injection of this peptide into the brain. Adjusted fetal MAP against amniotic pressure was also increased by icv ANG II, associated with increased c-fos in the central putative cardiovascular area--the paraventricular nuclei (PVN). Application of ANG II also induced intense c-fos expression in the supraoptic nuclei (SON), accompanied by a significant increase of fetal plasma vasopressin (AVP) levels, while maternal blood pressure (BP) and plasma AVP concentration were not changed. These results indicate that the central ANG II-mediated pressor response is functional at the last third of gestation, acting at the sites consistent with the cardiovascular neural network in the hypothalamus.Developmental Brain Research 12/2003; 145(2):169-76. · 1.78 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2013
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Soochow University (PRC)
Suzhou, Jiangsu Sheng, China
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2006–2012
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Beijing Sport University
Beijing, Beijing Shi, China
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2005
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University of California, Los Angeles
Los Angeles, CA, USA
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2004
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Harbor-UCLA Medical Center
Torrance, CA, USA
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