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ABSTRACT: AIMS: Salusin-β is a bioactive peptide with peripheral hypotensive, mitogenic and pro-atherosclerotic effects. The present study was designed to determine the roles of salusin-β in the paraventricular nucleus (PVN) and its relationship with arginine vasopressin (AVP) in hypertension and sympathetic activation. METHODS AND RESULTS: Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male Sprague-Dawley rats. Acute experiments were carried out 4 weeks after 2K1C or sham-operation under urethane and alpha-chloralose anaesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded. Microinjection of salusin-β into the PVN increased the RSNA, MAP, and HR in a dose-related manner, whereas anti-salusin-β IgG in the PVN decreased the RSNA and MAP, and abolished the effects of salusin-β in 2K1C rats. However, either salusin-β or anti-salusin-β IgG in the PVN failed to cause any significant effects in sham-operated rats. The number of salusin-β-like immunopositive neurons in the PVN was significantly increased in 2K1C rats. Salusin-β in the PVN increased the plasma AVP and norepinephrine levels in 2K1C rats, but not in sham-operated rats. Iv injection of dTyr(CH2)5(Me)AVP (an AVP V1-receptor antagonist, AAVP) decreased RSNA and MAP, and abolished the effects of salusin-β in the PVN in 2K1C rats. Microinjection of AAVP into the rostral ventrolateral medulla (RVLM), but not into the PVN, abolished the effects of salusin-β on RSNA and HR. CONCLUSION: Salusin-β in the PVN increases blood pressure, heart rate, and sympathetic outflow via both circulating AVP and AVP in the RVLM in hypertensive rats.
Cardiovascular research 03/2013; · 5.80 Impact Factor
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ABSTRACT: We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.
Hypertension 10/2012; 60(5):1280-6. · 6.21 Impact Factor
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ABSTRACT: Cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation. The present study was designed to investigate the contribution of enhanced CSAR to sympathetic activation in the early stage of diabetes and the involvement of AT(1) receptors in the paraventricular nucleus (PVN). Diabetes was induced by a single intravenous injection of streptozotocin in rats. Acute experiments were carried out under anesthesia after 3 wk. The CSAR was evaluated by the responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin or bradykinin. Sympathetic activity and CSAR were enhanced in diabetic rats. Plasma norepinephrine and angiotensin II were increased, but the transient receptor potential vanilloid 1 (TRPV1) in the left ventricle wall was not significantly increased in diabetic rats. Pericardial injection of resiniferatoxin to desensitize cardiac afferents or PVN microinjection of lidocaine attenuated the CSAR and decreased the RSNA and MAP in diabetic rats. The AT(1) receptor expression in the PVN increased in diabetic rats. Angiotensin II in the PVN caused greater increases in the RSNA and MAP and enhancement in the CSAR in diabetic rats, which were abolished by the losartan pretreatment. Losartan decreased the RSNA and MAP and attenuated the CSAR in diabetic rats but not in control rats. These results indicate that the CSAR is enhanced in the early stage of diabetic rats, which contributes to the sympathetic activation. AT(1) receptors in the PVN are involved in the enhanced CSAR in diabetic rats.
Journal of Applied Physiology 05/2012; 113(1):47-55. · 3.75 Impact Factor
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ABSTRACT: Injection of leptin into white adipose tissue (WAT) increases sympathetic outflow. The present study was designed to determine the effects of capsaicin and other chemicals in WAT on the sympathetic outflow and blood pressure and the roles of WAT afferents and hypothalamic paraventricular nucleus (PVN) in the adipose afferent reflex (AAR). The AAR was induced by injection of capsaicin, bradykinin, adenosine, adenosine triphosphate (ATP), or leptin into inguinal WAT (iWAT) or retroperitoneal WAT (rWAT) in anesthetized rats. The iWAT injection of capsaicin increased the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) but not the heart rate. Bradykinin, adenosine, or leptin but not ATP in the iWAT caused similar effects to capsaicin on the RSNA and MAP. Intravenous, intramuscular, or intradermal injection of capsaicin had no significant effects on the RSNA and MAP. The effects of capsaicin in rWAT were similar to that in iWAT on the RSNA and MAP. Furthermore, injection of capsaicin into the iWAT increased the WAT afferent nerve activities, WAT efferent nerve activity, and brown adipose tissue efferent nerve activity. The iWAT denervation or chemical lesion of the PVN neurons with kainic acid abolished the AAR induced by the iWAT injection of capsaicin. These results indicate that the stimulation of iWAT afferents with capsaicin, bradykinin, adenosine, or leptin reflexly increases the RSNA and blood pressure. The iWAT afferents and the PVN are involved in the AAR induced by capsaicin in the iWAT.
Journal of Applied Physiology 01/2012; 112(6):1008-14. · 3.75 Impact Factor
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ABSTRACT: Cardiac sympathetic afferent reflex (CSAR) is a positive-feedback, sympathoexcitatory reflex. Paraventricular nucleus (PVN) is an important component of the central neurocircuitry of the CSAR. The present study is designed to determine whether endothelin-1 (ET-1) in the PVN modulates the CSAR and sympathetic activity, and whether superoxide anions are involved in modulating the effects of ET-1 in the PVN in rats.
In anaesthetized Sprague-Dawley rats with cervical vagotomy and sinoaortic denervation, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the responses of the RSNA and MAP to epicardial application of capsaicin. Microinjection of ET-1 into the bilateral PVN dose-dependently enhanced the CSAR, increased the baseline RSNA and MAP. The effects of ET-1 were blocked by PVN pretreatment with the ET(A) receptor antagonist BQ-123. However, BQ-123 alone had no significant effects on the CSAR, the baseline RSNA and MAP. Bilateral PVN pretreatment with either superoxide anion scavenger tempol or polyethylene glycol-superoxide dismutase (PEG-SOD) inhibited the effects of ET-1 on the CSAR, RSNA and MAP. Microinjection of ET-1 into the PVN increased the superoxide anion level in the PVN, which was abolished by PVN pretreatment with BQ-123. Epicardial application of capsaicin increased superoxide anion level in PVN which was further enhanced by PVN pretreatment with ET-1.
Exogenous activation of ET(A) receptors with ET-1 in the PVN enhances the CSAR, increases RSNA and MAP. Superoxide anions in PVN are involved in the effects of ET-1 in the PVN.
PLoS ONE 01/2012; 7(7):e40748. · 4.09 Impact Factor
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ABSTRACT: Intracerebroventricular infusion of NaHS, a hydrogen sulfide (H(2)S) donor, increased mean arterial pressure (MAP). This study was designed to determine the roles of H(2)S in the paraventricular nucleus (PVN) in modulating sympathetic activity and cardiac sympathetic afferent reflex (CSAR) in chronic heart failure (CHF).
CHF was induced by left descending coronary artery ligation in rats. Renal sympathetic nerve activity (RSNA) and MAP were recorded under anesthesia. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of low doses of a H(2)S donor, GYY4137 (0.01 and 0.1 nmol), had no significant effects on RSNA, MAP and CSAR. High doses of GYY4137 (1, 2 and 4 nmol) increased baseline RSNA, MAP and heart rate (HR), and enhanced CSAR. The effects were greater in CHF rats than sham-operated rats. A cystathionine-β-synthase (CBS) inhibitor, hydroxylamine (HA) in PVN had no significant effect on the RSNA, MAP and CSAR. CBS activity and H(2)S level in the PVN were decreased in CHF rats. No significant difference in CBS level in PVN was found between sham-operated rats and CHF rats. Stimulation of cardiac sympathetic afferents with capsaicin decreased CBS activity and H(2)S level in the PVN in both sham-operated rats and CHF rats.
Exogenous H(2)S in PVN increases RSNA, MAP and HR, and enhances CSAR. The effects are greater in CHF rats than those in sham-operated rats. Endogenous H(2)S in PVN is not responsible for the sympathetic activation and enhanced CSAR in CHF rats.
PLoS ONE 01/2012; 7(11):e50102. · 4.09 Impact Factor
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ABSTRACT: The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributes to the pathogenesis and progression of hypertension. Activation of AT(1) receptors by angiotension (Ang) II in the paraventricular nucleus (PVN) augments the enhanced CSAR and sympathetic outflow in hypertension. The present study is designed to determine whether Ang-(1-7) in PVN plays the similar roles as Ang II and the interaction between Ang-(1-7) and Ang II on CSAR in renovascular hypertension.
The two-kidney, one-clip (2K1C) method was used to induce renovascular hypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardial application of capsaicin in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. Either Ang II or Ang-(1-7) in PVN caused greater increases in RSNA and MAP, and enhancement in CSAR in 2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT(1) receptor antagonist losartan induced opposite effects to Ang-(1-7) or Ang II respectively in 2K1C rats, but losartan had no effects in Sham rats. Losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatment with Ang-(1-7) dose-dependently augmented the RSNA, MAP, and CSAR responses to the Ang II in 2K1C rats. Ang II level, AT(1) receptor and Mas receptor protein expression in PVN increased in 2K1C rats compared with Sham rats but Ang-(1-7) level did not.
Ang-(1-7) in PVN is as effective as Ang II in enhancing the CSAR and increasing sympathetic outflow and both endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension. Ang-(1-7) in PVN potentiates the effects of Ang II in renovascular hypertension.
PLoS ONE 01/2012; 7(12):e52557. · 4.09 Impact Factor
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ABSTRACT: Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.
Experimental physiology 03/2011; 96(3):295-304. · 3.17 Impact Factor
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ABSTRACT: Cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation and angiotensin II (Ang II) in paraventricular nucleus (PVN) augments the CSAR in vagotomized (VT) and baroreceptor denervated (BD) rats with chronic heart failure (CHF). This study was designed to determine whether it is true in intact (INT) rats with CHF and to determine the effects of cardiac and baroreceptor afferents on the CSAR and sympathetic activity in CHF.
Sham-operated (Sham) or coronary ligation-induced CHF rats were respectively subjected to BD+VT, VT, cardiac sympathetic denervation (CSD) or INT. Under anesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded, and the CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Either CSAR or the responses of RSNA, MAP and CSAR to Ang II in PVN were enhanced in CHF rats treated with BD+VT, VT or INT. Treatment with VT or BD+VT potentiated the CSAR and the CSAR responses to Ang II in both Sham and CHF rats. Treatment with CSD reversed the capsaicin-induced RSNA and MAP changes and the CSAR responses to Ang II in both Sham and CHF rats, and reduced the RSNA and MAP responses to Ang II only in CHF rats.
The CSAR and the CSAR responses to Ang II in PVN are enhanced in intact CHF rats. Baroreceptor and vagal afferent activities inhibit CSAR and the CSAR responses to Ang II in intact Sham and CHF rats.
PLoS ONE 01/2011; 6(10):e25784. · 4.09 Impact Factor
