Acute cardiovascular effects of two central phenylethanolamine-N-methyl-transferase inhibitors in unanesthetized desoxycorticosterone-salt hypertensive rats.
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.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D003900:Desoxycorticosterone; C028625:LY 134046; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D010625:Phenylethanolamine N-Methyltransferase