Involvement of vasopressin in the cardiovascular effects of intracerebroventricularly administered alpha 1-adrenoceptor agonists in the conscious rat.
To determine the interaction between central adrenergic and vasopressinergic mechanisms in the regulation of cardiovascular function, the effects of intracerebroventricular (i.c.v.) administration of the alpha 1-agonists, methoxamine and phenylephrine, in conscious Long-Evans (LE) rats were compared with those in Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI). In LE rats, both i.c.v. methoxamine and phenylephrine increased mean arterial pressure (MAP) and decreased heart rate (HR) in a dose-related manner, while they had no effect on MAP and HR in DI rats within the dose range of 3-30 micrograms/kg. Both i.c.v. methoxamine (10 micrograms/kg) and phenylephrine (30 micrograms/kg) also increased plasma levels of arginine vasopressin (AVP) in LE rats from 2.6 +/- 0.4 (n = 9) to 22.4 +/- 3.5 (n = 6, P less than 0.01) and 37.0 +/- 4.0 pg/ml (n = 6, P less than 0.01), respectively, without affecting plasma renin activity (PRA) and plasma angiotensin II (ANG II) levels. Central alpha 1-adrenoceptor stimulation increases vasopressin release from the posterior pituitary, which in part is responsible for the hypertensive and bradycardic responses. However, central vasopressinergic pathways have also been shown to be involved in these cardiovascular effects. Neither i.c.v. nor intravenous (i.v.) infusion of AVP restored the cardiovascular response to i.c.v. alpha 1-agonists in DI rats. In LE rats, however, i.v. pretreatment with the specific vascular antagonist to the pressor effect of AVP, d(CH2)5Tyr(Me)AVP (VP-ANT; 10 micrograms/kg), significantly attenuated, but did not completely block the hypertensive and bradycardic effects of i.c.v. methoxamine and phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hiwatari
M
M
Johnston
C I
CI
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003243:Consciousness; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011910:Rats, Brattleboro; D011917:Rats, Inbred Lew; D014667:Vasopressins / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D014667:Vasopressins; D001127:Arginine Vasopressin; D010656:Phenylephrine; D001285:Atropine; D008729:Methoxamine