Characterization of lnhibition by Nifedipine and Nitroprusside of the Pressor Respones to alpha1-Adrenoceptor Agonists Cirazoline and Sgd 101/75 in Pithed Rats.
10.3349/ymj.1988.29.2.176
- Author:
Hyun Ok JUNG
1
;
Ki Whan HONG
Author Information
1. Department of Pharmacology, College of Medicine Pusan National University, Pusan, Korea.
- Publication Type:Original Article ; Comparative Study
- Keywords:
Calcim antagonists;
alpha1-Adrenoceptors
- MeSH:
Animal;
Blood Pressure/*drug effects;
Clonidine/*analogs and derivatives/antagonists and inhibitors/pharmacology;
Comparative Study;
Ferricyanides/*pharmacology;
Imidazoles/antagonists and inhibitors/*pharmacology;
Male;
Nifedipine/*pharmacology;
Nitroprusside/*pharmacology;
Rats;
Rats, Inbred Strains;
Vasoconstriction/*drug effects
- From:Yonsei Medical Journal
1988;29(2):176-184
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study the effects of two unrelated vasodilators, nifedipine and nitroprusside, on the pressor responsiveness to the 1-adrenoceptor full agonist cirazoline and partial agonist Sgd 101/75 in pithed rats were examined. The experiments were performed on the vasoconstriction which was mediated by newly synthetized 1-adrenoceptors after removal of existing 1-adrenoceptors by phenoxybenzamine treatment(5mg/kg, i. p.). The t1/2 for recovery of the maximum response and ED50 of cirazoline were 23.1 +/- 5.5 and 26.9 +/- 7.4 hours, respectively, while that for recovery of the maximum response of Sgd 101/75 was 59.2 +/- 18.9 hours. The relationship between the pressor response and the fractional receptor occupancy for cirazoline showed a rectangular hyperbola. This occupancy-response curve markedly shifted to the right one day after phenoxybenzamine and subsequently returned to the control, indicative of a large receptor reserve. However, for Sgd 101/75 the occupancy-response curve exerted less of a hyperbola and shifited little after phenoxybenzamine. While the maximum response to cirazoline in the control rats was resistant to inhibition by the calcium entry blocker nifedipine, this resistance was significantly reduced one and 3 days after phenoxybenzamine, just as the maximum response to Sgd 101/75 was sensitive to nifedipine in the control rats. Likewise, when nitroprusside was used instead, the results were similar for the cirazoline and Sgd 101/75 effects. In summary, it seems unlikely that the resistance to the calcium entry blocker of the full agonist effect can be wholly ascribed either to the receptor reserves or to the differential calcium utilization itself. Alternatively, it is suggested that the differential resistance to calcium antagonists can result from the magnitude of the variables involved in the activation of 1-adrenoceptor coupling processes depending on the full or partial agonist.
