An analysis of the inhibitory effects of prazosin on the phenylephrine response curves of the rat aorta.

On the endothelium-intact rat aorta some studies have shown prazosin to cause nonparallel rightward shifts of α-adrenoceptor agonist response curves. The aim of the present study was to analyze the inhibitory effect of prazosin on the phenylephrine responses of the endothelium-intact and endothelium-denuded rat aorta. Firstly I used phenoxybenzamine treatment to characterize the phenylephrine responses. The K values for phenylephrine were 0.13-0.18 μM and 0.07-0.16 μM in the endothelium-intact and endothelium-denuded rat aorta, respectively. In order to produce maximal responses of the endothelium-intact or - denuded preparation, phenylephrine had to occupy 95-99% of the α-adrenoceptors. Secondly I compared the inhibitory effects of phentolamine and prazosin on the endothelium-intact rat aorta. Phentolamine at 0.1 and 1 μM caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses (phentolamine pA = 7.9). The inhibitory effects of phentolamine were readily reversible. Prazosin at 0.1-10 nM caused nonparallel rightward shifts of the phenylephrine response curves with a depression of the maximal response. These inhibitory effects of prazosin were either irreversible or only very slowly reversible in drug-free solution and slowly reversible in the presence of phentolamine. Ninety min was required for the inhibitory effect of prazosin to reach equilibrium whereas phentolamine was at equilibrium after 45 min. Finally I have characterized the inhibitory actions of prazosin on the endothelium-denuded rat aorta. Prazosin caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses. The inhibitory effects of prazosin were at equilibrium after 45 min and were readily reversible. In conclusion prazosin is a readily reversible α-adrenoceptor antagonist in the endothelium-denuded but not in the endothelium-intact rat aorta. It seems likely that the endothelium accumulates or binds prazosin strongly so that the inhibitory action of prazosin is apparently slowly reversible in the endothelium-intact rat aorta. [ABSTRACT FROM AUTHOR]

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