Importance of endogenous vasopressin in the hypertensive and bradycardic response to central alpha 1-adrenergic stimulation.
To determine the interaction between alpha 1-adrenergic and vasopressinergic mechanisms in the central regulation of cardiovascular functions, the effects of intracerebroventricular (i.c.v.) administration of the alpha 1-agonists, methoxamine and phenylephrine, were examined in conscious Long-Evans (LE) rats and Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In LE rats, i.c.v. methoxamine and phenylephrine (3-30 micrograms/kg) increased blood pressure and decreased heart rate in a dose-related manner, while they had no detectable cardiovascular effects in DI rats. Neither i.c.v. (0.5 ng/kg per min, 1 h) nor intravenous (i.v., 2 ng/kg per min, 2 h) infusion of vasopressin (AVP) restored the cardiovascular response to i.c.v. phenylephrine in DI rats. In LE rats, however, i.v. pretreatment with the specific antagonist to the pressor effect of AVP, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), attenuated the hypertensive and bradycardic effects of i.c.v. phenylephrine, while i.c.v. pretreatment with AVP antagonist (300 ng/kg) did not alter the cardiovascular response to i.c.v. alpha 1-agonist. The cardiovascular response to i.c.v. phenylephrine was blocked by i.c.v. pretreatment with the alpha 1-antagonist, prazosin (2 micrograms/kg). Intracerebroventricular phenylephrine increased plasma AVP levels 14-fold without affecting plasma angiotensin II levels. The present study clearly demonstrated that endogenous AVP plays a significant role in the cardiovascular response to i.c.v. alpha 1-agonist.
Hiwatari
M
M
Johnston
C I
CI
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D001127:Arginine Vasopressin; D010656:Phenylephrine; D008729:Methoxamine