The interrelationship between the effects of captopril and nifedipine on pressor responses elicited by selective alpha-adrenoceptor agonists in the pithed rat preparation.
The interrelationship between the effects of the angiotensin converting enzyme inhibitor captopril and the calcium channel antagonist nifedipine on alpha-mediated vasoconstriction elicited by the administration of the full and partial alpha 1-adrenoceptor agonists St 587 and cirazoline, respectively, and the alpha 2-adrenoceptor agonist B-HT 920 were examined in pithed normotensive rats. Treatment with captopril was found to attenuate pressor responses produced by the administration of either alpha 1- or alpha 2-adrenoceptor agonists, resulting in the displacement to the right of the agonist dose-response curves and significantly increasing the calculated ED50 values. The maximum response was unaltered and the calculated dose ratios for alpha-agonists in the presence or absence of captopril were found to be 3, 4.6, and 3.8 for B-HT 920, St 587, and cirazoline, respectively. In comparison, nifedipine displaced the dose-response curves for all three alpha-agonists to the right but only significantly increased the ED50 values for the partial alpha 1-agonist St 587 and the alpha 2-agonist B-HT 920, with the calculated dose ratios being 3.2 and 3.8, respectively. Following treatment with nifedipine, however, the maximum responses were significantly reduced. A combination of captopril and nifedipine did not result in any significant additive increase in the ED50 values compared to those obtained with captopril or nifedipine alone. However, the inhibition of the maximum response to B-HT 920 by a combination of captopril and nifedipine was additive.(ABSTRACT TRUNCATED AT 250 WORDS)
Tabrizchi
R
R
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Alberta, Canada.
Triggle
C R
CR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003655:Decerebrate State; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007093:Imidazoles; C030655:St 587; C024763:talipexole; D002216:Captopril; D009543:Nifedipine; D003000:Clonidine; C014282:cirazoline