These results suggest that beta-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta 2-adrenergic receptors and are dependent on nitric oxide synthesis.

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Background — Increasing extracellular K + concentration within and just above the physiological range hyperpolarizes and relaxes vascular smooth muscle in vitro. These actions involve inwardly rectifying potassium channels (K IR ) and Na + /K + ATPase, which are inhibited, respectively, by Ba 2+ and ouabain. The role (if any) of K IR in controlling human resistance vessel tone is unknown, and we investigated this in the forearm. Methods and Results — Blood flow was measured by plethysmography in healthy men. Drugs and electrolytes were infused through the brachial artery. BaCl 2 (4 μmol/min, also used in subsequent experiments) increased Ba 2+ plasma concentration in the infused forearm to 50±0.8 μmol/L (mean±SEM) and reduced blood flow by 24±4% (n=8, P <0.001) without causing systemic effects. Ouabain (2.7 nmol/min), alone and with BaCl 2 , reduced flow by 10±2% and 28±3%, respectively (n=10). Incremental infusions of KCl (0.05, 0.1, and 0.2 mmol/min) increased flow from baseline by 1.0±0.2, 2.0±0.4, and 4.2±0.5 mL/min per deciliter forearm, respectively. Responses to KCl (0.2 mmol/min) were inhibited by BaCl 2 , alone and plus ouabain, by 60±9% and 88±6%, respectively (both P ≤0.01). In control experiments, norepinephrine (240 pmol/min) reduced blood flow by 24±2% but had no significant effect on K + -induced vasodilation. BaCl 2 , alone or with ouabain, did not significantly influence responses to verapamil or nitroprusside. Conclusions — Ba 2+ increases forearm vascular resistance. K + -induced vasodilation is selectively inhibited by Ba 2+ and almost abolished by Ba 2+ plus ouabain, suggesting a role for K IR and Na + /K + ATPase in controlling basal tone and in K + -induced vasorelaxation in human forearm resistance vessels.

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1 N G -monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2 This study sought to determine doses of L-NMMA that are maximally e ective in reducing basal and stimulated forearm blood¯ow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11 ± 330 nmol min 71 ) was compared with albuterol (0.33 ± 10 nmol min 71 ), and nitroprusside (1.7 ± 20 nmol min 71 ).3 The e ect of L-NMMA on basal¯ow approached maximum (53+2% reduction) at a dose of 16 mmol min 71 . L-NMMA (16 mmol min 71 ) did not signi®cantly in¯uence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P50.001, by repeated measures analysis of variance). 4 Inhibition of acetylcholine by L-NMMA (16 mmol min 71 ) was strongly in¯uenced by acetylcholine dose (73+7% inhibition at 11 nmol min 71 , P50.01; 4+11% inhibition at 330 nmol min 71 , P=NS, Student's paired t-test). Signi®cant inhibition of albuterol was observed at all doses. 5 A higher dose of L-NMMA (64 mmol min 71 ) did not signi®cantly inhibit the response to acetylcholine (330 nmol min 71 ). Responses to this dose of acetylcholine were una ected by a cyclooxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42+19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.