Functional involvement of vasopressin in the maintenance of systemic arterial blood pressures after phenoxybenzamine or phentolamine administration: studies in Long-Evans and Brattleboro rats.
The alpha adrenoceptor antagonists phenoxybenzamine and phentolamine are reported to have opposite effects on vasopressin release, the former inhibiting and the latter enhancing it. In this study we have assessed the functional involvement of vasopressin in the maintenance of blood pressure in conscious rats after administration of either phenoxybenzamine or phentolamine. In normal (Long-Evans) rats, phenoxybenzamine caused a small fall in arterial blood pressure, whereas phentolamine initially caused a profound hypotension which was followed by a fluctuating recovery back to normotensive levels. Similar effects were seen in rats deficient in hypothalamic vasopressin (Brattleboro strain). Administration of an antagonist of the cardiovascular actions of vasopressin [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-8-D-arginine vasopressin] in the presence of either alpha adrenoceptor antagonist alone was without effect in Long-Evans or Brattleboro rats, but, under these conditions, subsequent administration of captopril caused a profound and sustained hypotension in both strains. Administration of captopril in the presence of either alpha adrenoceptor antagonist alone caused a prompt fall in blood pressure which was sustained for the duration of the experiment in the Brattleboro rats. However, under these conditions, the blood pressure of the Long-Evans rats showed some recovery over the subsequent 45 min; this recovery was antagonized by [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-8-D-argine vasopressin]. It is concluded that after alpha adrenoceptor antagonism with either phenoxybenzamine or phentolamine, the renin-angiotensin system exerts a major pressor influence. However, after captopril administration in the presence of phenoxybenzamine or phentolamine, vasopressin contributes to the maintenance of arterial blood pressure in Long-Evans rats; the magnitude of this contribution is similar irrespective of the alpha adrenoceptor antagonist used.
Winn
M J
MJ
Gardiner
S M
SM
Bennett
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro / Q000502:physiology*; D011922:Rats, Mutant Strains / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D010643:Phenoxybenzamine; D014667:Vasopressins; D001127:Arginine Vasopressin; C025044:argipressin, beta-mercapto-beta,beta cyclopentamethylenepropionic acid(1)-; D002216:Captopril; D010646:Phentolamine