title: Endothelin-1 and vascular tone in subjects with atherogenic risk factors.
abstract: Endothelin-1 (ET-1) is a potent vasoconstrictor that increases vascular tone in the resistance vessels of subjects with hypertension. It is unclear whether endogenous ET-1 affects resistance-vessel function equally in patients with other cardiovascular risk factors. Vasoconstriction to ET-1 is mediated principally via the endothelin-A (ETA) receptor on vascular smooth muscle cells. Accordingly, we used an ETA-specific antagonist, BQ-123, to test the hypothesis that endogenous ET-1 increases vascular resistance selectively in subjects with hypertension compared with other risk factors. BQ-123 was infused at 100 nmol/min for 80 minutes into the brachial artery of 10 subjects with hypertension (mean+/-SEM arterial pressure, 106+/-5 mm Hg), 12 subjects with hypercholesterolemia (mean+/-SEM total cholesterol, 7.1+/-0.2 mmol/L), 10 active smokers (mean+/-SEM, 42+/-11 pack-years), and 11 healthy, age-matched individuals. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. BQ-123 dilated resistance arterioles in hypertensive subjects, with FBF's increasing by 46+/-7% from baseline (P<0.001). BQ-123 increased FBF to a lesser extent in hypercholesterolemic (24+/-5%, P<0.001) and healthy (20+/-8%, P=0.007) individuals but did not affect FBF significantly in smokers (10+/-8%, P=0.185). The vasodilator response in hypertensive subjects, but not in hypercholesterolemic patients or smokers, was significantly greater than that in healthy individuals (P=0.012). Endogenous ET-1, acting via the ETA receptor, increases resistance-vessel tone in subjects with hypertension more than in subjects with hypercholesterolemia or in smokers. These results indicate that ET-1 contributes more to the pathophysiology of hypertension than of other risk factors in subjects without overt atherosclerosis.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Nohria
authors.forename: Leslie
authors.initials: L
authors.lastname: Garrett
authors.forename: Wendy
authors.initials: W
authors.lastname: Johnson
authors.forename: Scott
authors.initials: S
authors.lastname: Kinlay
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D001161:Arteriosclerosis / Q000209:etiology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000209:etiology / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A; D012039:Regional Blood Flow / Q000187:drug effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014655:Vascular Resistance; D014664:Vasodilation
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)