caa a22 4500 469078200 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00173542 doi (NATIONALLICENCE)springer-10.1007/BF00173542 Doggrell Sheila Department of Pharmacology, School of Medicine, University of Auckland, Private Bag, Auckland, New Zealand aut An analysis of the inhibitory effects of prazosin on the phenylephrine response curves of the rat aorta [Elektronische Daten] [Sheila Doggrell] Summary: On the endothelium-intact rat aorta some studies have shown prazosin to cause nonparallel rightward shifts of α1-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 KA 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 α1-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 pA2 = 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 α1-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. Springer-Verlag, 1992 Prazosin nationallicence Phentolamine nationallicence Phenoxybenzamine nationallicence Phenylephrine nationallicence α1-Adrenoceptor reserve nationallicence Rat aorta nationallicence Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 294-302 0028-1298 346:3<294 1992 346 210 https://doi.org/10.1007/BF00173542 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00173542 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Doggrell Sheila Department of Pharmacology, School of Medicine, University of Auckland, Private Bag, Auckland, New Zealand aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 294-302 0028-1298 346:3<294 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer