Vascular α1-Adrenoceptor Subtype Selectivity and α1-Blocker-Induced Orthostatic Hypotension

Access this Article

Author(s)

    • HIRASAWA Akira
    • Department of Molecular, Cell Pharmacology, National Children 's Medical Research Center
    • IKEGAKI Ichiro
    • First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical Industry
    • ASANO Toshio
    • First Laboratory for Pharmacological Research, Institute for Life Science Research, Asahi Chemical Industry
    • TAKADA Tatsuyuki
    • Department of Molecular, Cell Pharmacology, National Children 's Medical Research Center
    • TSUJIMOTO Gozoh
    • Department of Molecular, Cell Pharmacology, National Children 's Medical Research Center

Abstract

Newly developed α<SUB>1</SUB>-adrenoceptor antagonists including naftopidil are free from the “prazosin-like” side effect of orthostatic hypotension and associated symptoms. We investigated the mechanism for the differential effects of naftopidil and prazosin on the development of postural hypotension, with special attention on their selectivity for the α<SUB>1</SUB>-adrenoceptor subtype. We observed that head-up tilt caused a similar extent of drop in mean arterial pressure in control, naftopidil (1 mg/kg)- or prazosin (10 μg/kg)-treated rats; however, the tilt-induced postural hypotension was recovered within 2 min in the naftopidil-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 potent in the portal vein, while prazosin showed similar potency in both tissues. Reverse transcription-polymerase chain reaction analysis showed that the expression of α<SUB>1d</SUB>-adrenoceptor mRNA predominated in the aorta, while that of α<SUB>1b</SUB>-adrenoceptor mRNA predominated in the portal vein. Using cloned rat α<SUB>1</SUB>-adrenoceptor subtypes, we found that naftopidil was selective for the α<SUB>1d</SUB>-subtype with approximately ninefold higher affinity than at the other subtypes. These results show that the pharmacological character of naftopidil, combined with the differential expression of the α<SUB>1</SUB>-adrenoceptor subtype in the artery and the vein, may partly explain the differential effect of naftopidil and prazosin on head-up tilt-induced hemodynamic responses.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 77(1), 61-70, 1998-05-01

    The Japanese Pharmacological Society

References:  30

Cited by:  4

Codes

  • NII Article ID (NAID)
    10008680181
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4503675
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top