title: Forearm vasoconstriction in response to noradrenaline and NG-monomethyl-L-arginine in essential hypertension.
abstract: A role for abnormal NO production in essential hypertension remains controversial. Blunted vasoconstriction of forearm resistance vasculature in response to N(G)-monomethyl-L-arginine (L-NMMA; an inhibitor of NO biosynthesis), relative to the response to noradrenaline, has been reported in hypertensive patients and interpreted as evidence of reduced basal NO biosynthesis. We sought to determine whether reduced sensitivity of forearm vasculature to the vasoconstrictor action of L-NMMA relative to that of noradrenaline is a consistent finding in essential hypertension. We studied a group of patients (n=32; blood pressure 176+/-4/102+/-2 mmHg; means+/-S.E.M.) and a group of healthy normotensive controls (n=32; blood pressure 130+/-2/75+/-1 mmHg). Noradrenaline (60-240 pmol.min(-1)) and L-NMMA (1-4 micromol.min(-1)) were infused into the brachial artery, and forearm blood flow was measured by venous occlusion plethysmography. The effects of each vasoconstrictor were similar in hypertensive and control subjects. The highest dose of L-NMMA reduced forearm blood flow by 0.75+/-0.12 ml.min(-1).dl(-1) in the control group and by 0.89+/-0.10 ml.min(-1).dl(-1) in the hypertensive group. The study had 90% power (with P=0.05) to detect a 10% difference in forearm blood flow response between the hypertensive and control groups. We conclude that reduced sensitivity of forearm resistance vasculature to the vasoconstrictor action of L-NMMA is not a universal feature of essential hypertension. This argues against a primary role for reduced basal NO biosynthesis in skeletal muscle resistance vessels in the pathogenesis of essential hypertension.
authors.affiliation: Department of Clinical Pharmacology, Centre for Cardiovascular Biology and Medicine, King's College, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K.
authors.forename: B J
authors.initials: BJ
authors.lastname: Kneale
authors.forename: P J
authors.initials: PJ
authors.lastname: Chowienczyk
authors.forename: S E
authors.initials: SE
authors.lastname: Brett
authors.forename: J R
authors.initials: JR
authors.lastname: Cockcroft
authors.forename: J M
authors.initials: JM
authors.lastname: Ritter
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine