The effect of HN-65021 on responses to angiotensin II in human forearm vasculature.
We studied the effect of (2-butyl-4-chloro-1[[2'-(1H-tetrazol-5-yl) [1,1'-biphenyl]methyl]-1H-imadazole-5-carboxylic acid,-1-(ethoxycarbonyloxy) ethyl-ester (HN-65021), on angiotensin II induced vasoconstriction in forearm vasculature of eight healthy men. Placebo and HN-65021 (5, 10 and 100 mg) were administered orally. Forearm blood flow was measured by venous occlusion plethysmography during rising dose brachial artery infusions of angiotensin II (0.3-1000 pmol min-1) 2 h after dosing. HN-65021 inhibited angiotensin II, causing a shift to the right of the dose-response curve. Angiotensin II (100 pmol min-1) decreased mean blood flow in the infused arm by 63.1 +/- 3.2% when infused following placebo and by 49.9 +/- 4.3%, 50.7 +/- 3.5% and 36.4 +/- 2.8% following HN-65021 doses of 5.10 and 100 mg respectively. These results demonstrate that HN-65021 antagonises angiotensin II receptor mediated vasoconstriction in human forearm resistance vessels.
Cockcroft
J R
JR
Department of Clinical Pharmacology, UMDS St Thomas' Hospital, London, U.K.
Chowienczyk
P J
PJ
Brett
S E
SE
Mant
T G
TG
Durnin
C
C
Lynn
F
F
Stevenson
P
P
Ritter
J M
JM
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D001916:Brachial Artery / Q000187:drug effects*; D018592:Cross-Over Studies; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
C098801:HN 65021; D007093:Imidazoles; D011355:Prodrugs; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II