Acute cardiovascular effects of two central phenylethanolamine-N-methyl-transferase inhibitors in unanesthetized desoxycorticosterone-salt hypertensive rats

Eur J Pharmacol. 1984 Jul 20;102(3-4):515-9. doi: 10.1016/0014-2999(84)90573-9.

Abstract

SKF 64139, an inhibitor of phenylethanolamine-N-methyltransferase (PNMT), has a marked hypotensive effect in models of sodium-dependent hypertension. The mechanism of this effect is obscure, the compound having in addition alpha-adrenoceptor blocking properties. We compared the acute effects of SKF 64139 with those of LY 134046, another PNMT inhibitor with minimal alpha-blocking capacity, in desoxycorticosterone-salt hypertensive rats. The former agent produced profound hypotension whereas the latter caused only bradycardia. Both induced a similar pronounced suppression of PNMT activity in the C1 and C2 region of the medulla oblongata. These results suggest that the alpha-adrenergic effect rather than PNMT inhibition accounts for the acute lowering of blood pressure in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology*
  • Blood Pressure / drug effects
  • Brain / enzymology
  • Desoxycorticosterone
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Hypertension / chemically induced
  • Hypertension / physiopathology*
  • Isoquinolines / pharmacology*
  • Male
  • Phenylethanolamine N-Methyltransferase / antagonists & inhibitors*
  • Phenylethanolamine N-Methyltransferase / metabolism
  • Rats
  • Rats, Inbred Strains
  • Tetrahydroisoquinolines*

Substances

  • Benzazepines
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Desoxycorticosterone
  • LY 134046
  • 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline
  • Phenylethanolamine N-Methyltransferase