Interactions between the brain renin-angiotensin system and brain prostanoids in the control of vasopressin secretion.
ABSTRACT Experiments were carried out in conscious, unrestrained, male rats to evaluate possible interactions between brain prostanoids and the brain renin-angiotensin system in the control of vasopressin release and in cardiovascular regulation. The intracerebroventricular (icv) administration of prostaglandin D2 (PGD2) resulted in transient increases in the plasma vasopressin concentration (PAVP) and heart rate and a gradual increase in mean arterial blood pressure (MABP). Pretreatment icv with saralasin, an angiotensin II-receptor antagonist, moderately attenuated the vasopressin response to PGD2, but had no effect on the heart rate and blood pressure responses. Angiotensin II icv increased both PAVP and MABP. This vasopressin response was almost completely prevented by prior icv meclofenamate, a cyclooxygenase inhibitor, and the blood pressure response was attenuated. These observations, combined with previous studies of the role of central angiotensin II and central prostanoids in the physiological control of vasopressin release, suggest that there may be important interactions between brain prostanoids and the brain renin-angiotensin system in this control.
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ABSTRACT: Although the anteroventral third ventricular region (AV3V), a forebrain area essential for homeostatic responses, includes receptors for gamma-aminobutyric acid (GABA), the roles of these receptors in controlling vasopressin (AVP) secretion and related phenomena have not been clarified as yet. This study aimed to pursue this problem in conscious rats implanted with indwelling catheters. Cerebral injection sites were determined histologically. Applications of bicuculline, a GABA(A) receptor antagonist, to the AV3V induced prompt and marked augmentations in plasma AVP, osmolality, glucose, arterial pressure and heart rate, without affecting plasma electrolytes. Such phenomena did not occur when phaclofen, a GABA(B) receptor antagonist, was applied to the AV3V. All of the effects of AV3V-administered bicuculline were abolished by preadministration of the GABA(A) receptor agonist muscimol. Preadministration of either MK-801 or NBQX, ionotropic glutamatergic receptor antagonists, was also potent to abolish the AVP response to AV3V bicuculline. When hypertonic saline was infused intravenously, plasma AVP increased progressively, in parallel with rises in plasma osmolality, sodium and arterial pressure. AV3V application of muscimol or baclofen, a GABA(B) receptor agonist, was found to abolish the response of plasma AVP, without inhibiting that of the osmolality or sodium. The response of arterial pressure was also blocked by muscimol treatment, but not by baclofen treatment. Based on these results, we concluded that, under basal conditions, GABA receptors in the AV3V or vicinity may tonically operate to attenuate AVP secretion and cardiovascular functions through mechanisms associated with glutamatergic activity, and that plasma hyperosmolality may cause facilitation of AVP release by decreasing forebrain GABAergic activity.Brain research bulletin 09/2008; 77(1):61-9. · 2.97 Impact Factor
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ABSTRACT: The aim of this study was to investigate the roles of prostaglandins (PGs) in the anteroventral third ventricular region (AV 3V), a cerebral site for cardiovascular homeostasis, in hypovolemia-induced vasopressin (AVP) secretion. We infused meclofenamate (78. 3 nmol in 1 microl), a PG synthesis inhibitor, or PGE2 (7.1 nmol in 0.5 microl) into the AV 3V of conscious rats, examining their effects on plasma AVP and other variables in the presence or absence of hemorrhages. The hemorrhages (about 14% of blood volume) were conducted successively by taking femoral arterial blood over a 30-s period at 10-min intervals. The first hemorrhage increased plasma AVP in blood samples obtained 10 min later, without affecting plasma angiotensin II (ANG II), arterial pressure and heart rate. The second hemorrhage after 10 min raised plasma AVP further and, remarkably, augmented plasma ANG II, and reduced arterial pressure. The AVP responses to both the first and second hemorrhages were attenuated by meclofenamate infusion into the AV 3V performed 35 min before the first hemorrhage. The meclofenamate infusion did not alter the response of ANG II, while that of arterial pressure was potentiated and heart rate was decreased after the second hemorrhage. These effects of meclofenamate on plasma AVP and the cardiovascular parameters were not found when the drug was infused into the nucleus accumbens, the region slightly distant from the AV 3V, or the lateral cerebral ventricle. In the normovolemic state, meclofenamate administered into the three brain regions did not affect any of the variables monitored. In contrast, application of PGE2 into the AV 3V enhanced plasma AVP, heart rate and arterial pressure after 5 and 15 min. Histological examination indicated that infusion sites of meclofenamate in the AV 3V were close to those of PGE2 in several cases and included areas such as the organum vasculosum of the lamina terminalis, periventricular hypothalamic nucleus, and the median and medial preoptic nuclei. These results suggest that PGs synthesized in and/or near the AV 3V may be involved in the regulation of AVP release and cardiovascular function in the hypovolemic state.European Journal of Endocrinology 02/1998; 138(2):206-15. · 3.69 Impact Factor
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ABSTRACT: Cyclooxygenase (COX) derived prostanoids contribute to angiotensin II (AngII) hypertension (HTN). However the specific mechanisms by which prostanoids act are unclear. AngII-induced hypertension is caused partly by increased sympathetic nervous system activity, especially in a setting of high dietary salt intake (AngII-salt HTN). This study tested the hypothesis that COX-derived prostanoids cause AngII-salt sympathoexcitation and hypertension. Experiments were conducted in conscious rats. Infusion of AngII (150ng/kg/min sc) caused a marked hypertension in rats on 2% salt diet, but a much smaller increase in blood pressure in rats on 0.4% salt diet. The non-selective COX inhibitor ketoprofen (2 mg/kg sc) given throughout the AngII infusion period attenuated hypertension development in rats on 2% NaCl diet, but not in rats on 0.4% NaCl diet. The acute depressor response to ganglion blockade was used to assess neurogenic pressor activity in rats on 2% NaCl diet. Ketoprofen treated rats showed a smaller fall in arterial pressure in response to ganglion blockade during AngII infusion than did non-treated controls. In additional experiments, ketoprofen treated rats exhibited smaller increases in plasma norepinephrine levels and whole body norepinephrine spillover than we reported previously in AngII-salt HTN. Finally, the effects of the selective COX-1 inhibitor SC560 (10mg/kg/day ip) and the selective COX-2 inhibitor nimesulide (10mg/kg/day ip) were investigated. Treatment with SC560 but not nimesulide significantly reduced blood pressure and the depressor response to ganglion blockade in AngII-salt HTN rats. The results suggest that COX-1 products are critical for sympathoexcitation and the full development of AngII-salt HTN in rats.AJP Heart and Circulatory Physiology 09/2013; · 4.01 Impact Factor