Effect of the non peptide angiotensin II antagonist, GR117289C on the vasoconstrictor actions of angiotensin II in the human forearm.
OBJECTIVE
GR117289C is a non peptide, selective angiotensin (AT1) receptor antagonist. The purpose of this study was to determine whether this agent, given orally, could attenuate the vasoconstrictor effects of angiotensin II(AII) infused locally into the forearm circulation in man.


METHODS
Eight healthy male subjects were studied on four occasions in a randomized, double-blind, placebo controlled, crossover study. Five hours (approximate time of peak dynamic effect) following dosing with GR117289C (300 mg, 100 mg, 10 mg or placebo), A II was infused in incremental doses (0, 0.1, 0.4, 1.6, 6.2, 25 and 100 pmol min-1) into the left brachial artery, each for 10 min. Forearm blood flow was measured using venous occlusion plethysmography.


RESULTS
GR117289C inhibits the vasoconstrictor effects of A II in a dose dependent manner. The active treatment: placebo ratios of forearm blood flow in the infused arm during the highest dose of AII (100 pmol min-1) were: GR117289C 10 mg, 1.12 (95% C.I. 0.81-1.55; P = 0.478), 100 mg, 1.43 (95% C.I. 1.01-2.01; P = 0.042) and 300 mg, 1.62 (95% C.I. 1.17-2.24; P = 0.006). There was no significant difference in blood pressure between each of the treatment groups and placebo.


CONCLUSIONS
GR117289C is a pharmacologically active, oral A II antagonist in healthy men.
Lyons
D
D
Department of Medicine and Therapeutics, University of Aberdeen Medical School, Foresterhill Aberdeen.
Webster
J
J
Nixon
A
A
Young
M M
MM
Smith
J
J
Benjamin
N
N
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D057911:Angiotensin Receptor Antagonists; D009539:Nicotinic Acids; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C078790:GR 117289