Effect of endothelin blockade on basal and stimulated forearm blood flow in patients with essential hypertension.
Endothelin receptor antagonism lowers blood pressure in patients with essential hypertension, but the contribution of the endothelin system to increased vascular tone in these patients remains controversial. We used strain-gauge venous plethysmography to measure changes in basal and metabolically stimulated (peak reactive hyperemia [PRH]) forearm blood flow (FBF) induced by continuous intrabrachial infusion of SB 209670, a dual endothelin type A/endothelin type B receptor antagonist (ETRA) in 11 patients with hypertension and 12 healthy age-matched control subjects. In both groups, ETRA caused significant vasodilation (increase in FBF compared with baseline over the last 30 minutes of ETRA infusion: 75+/-12% in control subjects, 40+/-13% in hypertension patients; P<0.01 for both groups). By repeated-measures ANOVA, there was no greater increase in FBF after ETRA in hypertension patients compared with control subjects. In addition, FBF responses to PRH, expressed as percent change from baseline (prePRH), were similar in both groups (control subjects: preETRA, 1381+/-222%; during ETRA, 921+/-178%; and hypertension patients: preETRA, 1232+/-221%: during ETRA, 865+/-285%). We conclude that basal and stimulated vasodilation induced by short-term ETRA infusion in the forearm vasculature of hypertension patients is not increased compared with that of control subjects. An enhanced contribution of the endothelin system to vascular tone in hypertension patients could not be demonstrated using this experimental approach.
Martin
Paul
P
Clinical Pharmacology Unit, Department of Medicine, Monash University, Alfred Hospital, Melbourne, Australia.
Ninio
Daniel
D
Krum
Henry
H
D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007189:Indans / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-