Demonstration of the antihypertensive activity of phenyl-2-aminoethyl selenide.
The effect of phenyl-2-aminoethyl selenide (PAESe) on blood pressure and heart rate was examined in anesthetized dogs and spontaneously hypertensive rats (SHR) in order to assess its possible utility as an antihypertensive agent. PAESe was shown to be an indirect-acting sympathomimetic whose transient increase in blood pressure was blocked by cocaine. PAESe exhibited potent antihypertensive activity in SHR. This hypotensive activity was dose-dependent, was evident in both acute and chronic assays and occurred after i.v. or i.p. administration or slow release from subdermally implanted osmotic pumps. The hypotensive activity in SHR occurred concomitant with a reduction in heart rate and a reduction in total body weight. Hearts isolated from SHR treated daily for 2 weeks with PAESe were significantly reduced in weight and in total catecholamine content. An investigation of the nature of the body weight loss which accompanied chronic dosing suggested that PAESe also possessed an anorexigenic property distinct from its antihypertensive activity. An examination of plasma electrolytes, enzymes and other metabolites from chronically treated rats showed no obvious toxic effects of such dosing.
Pollock
S H
SH
School of Pharmacy, Mercer University, Atlanta, Georgia.
Herman
H H
HH
Fowler
L C
LC
Edwards
A S
AS
Evans
C O
CO
May
S W
SW
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D005021:Ethylamines / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D016566:Organoselenium Compounds; D051381:Rats; D011918:Rats, Inbred SHR; D013566:Sympathomimetics / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D004573:Electrolytes; D005021:Ethylamines; D016566:Organoselenium Compounds; D013566:Sympathomimetics; C056035:phenyl-2-aminoethylselenide