Inhibitors of phenylethanolamine-N-methyltransferase: effects on brain catecholamine content and blood pressure in DOCA-salt hypertensive rats.
Inhibitors [2-cyclooctyl-2-hydroxyethylamine (CONH), 1 aminomethylcycloundecanol (CUNH), 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF64139), 2,3-dichloro-alpha-methylbenzylamine (DCMB), 8,9-dichloro-2,3,4,5-tetrahydro-1H-2-benzazepine(LY134046)] of phenylethanolamine N-methyltransferase (PNMT) were found to reduce blood pressure in deoxycorticosterone-salt (DOCA-salt) hypertensive rats. CONH, CUNH and DCMB, but not SKF64139 and LY134046, also lowered blood pressure in normotensive control rats. All of the PNMT inhibitors tested lowered hypothalamic epinephrine (Epi) content in both DOCA-salt hypertensive and normotensive rats. DCMB, SKF64139 and LY134046 also lowered brainstem Epi in both animal groups. From these data a good correlation could not be made between the blood pressure lowering effects of PNMT inhibitors and their effects on hypothalamic Epi content as had been observed in other animal models of hypertension (e.g. spontaneously hypertensive rats).
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D003900:Desoxycorticosterone; D010625:Phenylethanolamine N-Methyltransferase