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Effect of Nicorandil, N-(2-Hydroxyethyl)nicotinamide Nitrate, a New Anti-Anginal Agent, on Contractile Responses to Alpha-1- and Alpha-2-Adrenoceptor Agonists in Isolated Rabbit Aorta

 

作者: Shoji Shibata,   Nobuhiro Satake,   Shoichi Ueda,   Kelly Hester,   Fidel Flores,  

 

期刊: Journal of Vascular Research  (Karger Available online 1986)
卷期: Volume 23, issue 4-5  

页码: 246-256

 

ISSN:1018-1172

 

年代: 1986

 

DOI:10.1159/000158645

 

出版商: S. Karger AG

 

关键词: Nicorandil;Nifedipine;Methoxamine;Clonidine;BHT-920;Phenoxybenzamine;Rabbit aorta;α-Adrenoceptors

 

数据来源: Karger

 

摘要:

Effects of nicorandil on contractile responses to α1- and α2adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10–6 or 10–5M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10–6 and 10–5M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10–5M) inhibited the residual response to MO, and nifedipine (10–5M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA2 of about 9) on MO and CL was much greater than that of yohimbine (pA2 of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca2+, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of α1-adrenoceptors. It is also suggested that nicorandil minimally affects voltage-dependent Ca2+ influx and that differential effects of nicorandil on the responses to α1 and α2 agonists may be the result of differeneces in the amount of receptor reserve that exist for MO, CL, and BHT-920 in t

 

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