Barium Reduces Resting Blood Flow and Inhibits Potassium-Induced Vasodilation in the Human Forearm

Abstract

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.

ATP‐induced vasodilation in human skeletal muscle

“…Ouabain infusion alone induced vasoconstriction, which has been reported before (Robinson et al, 1983;Tack et al, 1996;Dawes et al, 2002). Baseline activity of Na þ K þ -ATPase apparently contributes to resting vascular tone, probably by maintaining membrane polarity.…”

Block of Inward Rectifying K + Channels (K IR ) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature

“…[1][2][3] K IR channels play a role in K ϩ -mediated dilation of rat coronary and cerebral arteries 4 and contribute to basal vasodilator tone in human forearm resistance vasculature. 5 K IR is more sensitive to Ba 2ϩ than other K ϩ channels, half-block being achieved at 2 mol L Ϫ1 at Ϫ60 mV in rat cerebral artery vascular smooth muscle, 6 Ϸ50-times more potent than on K ATP channels, Ͼ500-times as potent as on K V channels, and Ͼ5000-times as potent as on K Ca channels. 7 Brachial artery infusion of barium chloride in a dose that increases the local mean plasma concentration of Ba 2ϩ to 50 mol L Ϫ1 inhibits the vasodilator response to infused potassium chloride by 60Ϯ9%.…”

Thiazide-Like Diuretics Attenuate Agonist-Induced Vasoconstriction by Calcium Desensitization Linked to Rho Kinase

“…Further, the barium-induced vasoconstriction was not significantly affected by chlorthalidone or hydrochlorothiazide (97Ϯ18% or 90Ϯ35%; each nϭ3; PϭNS), probably because barium directly causes depolarization and hence vasoconstriction. 19 Next, the effects of thiazide-like diuretics were compared with those of the specific Rho kinase inhibitor Y27632. In the presence or absence of endothelium, incubation of segments from rat aorta with 1 mol/L Y27632 significantly reduced the angiotensin II-induced vasoconstriction to 19Ϯ5% or 18Ϯ6% (each nϭ5; PϽ0.01 by ANOVA).…”