VASCULAR ALPHA(1)-ADRENOCEPTOR SUBTYPE SELECTIVITY AND ALPHA(1)-BLOCKER-INDUCED ORTHOSTATIC HYPOTENSION

Citation
H. Take et al., VASCULAR ALPHA(1)-ADRENOCEPTOR SUBTYPE SELECTIVITY AND ALPHA(1)-BLOCKER-INDUCED ORTHOSTATIC HYPOTENSION, Japanese Journal of Pharmacology, 77(1), 1998, pp. 61-70
Citations number
30
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00215198
Volume
77
Issue
1
Year of publication
1998
Pages
61 - 70
Database
ISI
SICI code
0021-5198(1998)77:1<61:VASSAA>2.0.ZU;2-1
Abstract
Newly developed alpha(1)-adrenoceptor antagonists including naftopidil are free from the ''prazosin-like'' side effect of orthostatic hypote nsion and associated symptoms. We investigated the mechanism for the d ifferential effects of naftopidil and prazosin on the development of p ostural hypotension, with special attention on their selectivity for t he alpha(1)-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftop idil (1 mg/kg)- or prazosin (10 mu g/kg)-treated rats; however, the ti lt-induced postural hypotension was recovered within 2 min in the naft opidil-treated group, but not in the prazosin-treated group. Comparing an inhibitory effect on noradrenaline-induced contraction in the rat aorta and portal vein, we found that naftopidil was sixfold less poten t in the portal vein, while prazosin showed similar potency in both ti ssues. Reverse transcription-polymerase chain reaction analysis showed that the expression of alpha(1d)-adrenoceptor mRNA predominated in th e aorta, while that of alpha(1d)-adrenoceptor mRNA predominated in the portal vein. Using cloned rat alpha(1)-adrenoceptor subtypes, we foun d that naftopidil was selective for the alpha(1d)-subtype with approxi mately ninefold higher affinity than at the other subtypes. These resu lts show that the pharmacological character of naftopidil, combined wi th the differential expression of the alpha(1)-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect o f naftopidil and prazosin on head-up tilt-induced hemodynamic response s.