Effect of Local Infusion of Ouabain on Human Forearm Vascular Resistance and on Response to Potassium, Verapamil and Sodium Nitroprusside

Robinson, B. F.; Phillips, R. J. W.; Wilson, P. N.; Chiodini, Peter L.

doi:10.1097/00004872-198308000-00009

Cited by 30 publications

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“…34 Because ouabain would have caused more depolarization and opened more calcium channels, we would have expected that ouabain could modulate the response to verapamil, a calcium channel blocker. In the current study, however, ouabain did not affect the response to verapamil, as in the previous study of Robinson et al 26 Therefore, the indirect implication from these data is that some other transport pathway for calcium, i.e., sodium-calcium exchange, is involved in the control of vascular tone by the sodium pump. This implication is supported by the recent experiment indicating that incubation of resistance arteries in ouabain to inhibit active sodium efflux increases the contractile response to caffeine stimulation by inhibition of sodium-calcium exchange activity.…”

Section: Discussionsupporting

confidence: 73%

Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans.

Fujita

Ito

1993

Hypertension

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To evaluate the role of the sodium pump in resistance control in vivo, we studied vascular responses to potassium, which produces vasodilation by the activation of vascular Na + ,K + -ATPase, in nonnotensive volunteers receiving a high salt diet compared with volume-depleted subjects receiving diuretic treatment Forearm blood flow was measured by strain-gauge plethysmography during small increments in local concentrations of potassium with intrabrachial arterial infusions of KCI. Infusions of 0.12 and 0.24 mEq/min KCI increased forearm blood flow and decreased forearm vascular resistance in a dosedependent fashion. But the simultaneous intrabrachial arterial infusion of 2 /ig/min ouabain, a Na + ,K + -ATPase inhibitor, could blunt the decremental response of vascular resistance to 0.12 mEq/min KCI. The decrements of vascular resistance with KCI infusions divided by the initial resistance were significantly less with ouabain compared with those without ouabain (43±4% versus 57±3%, p<0.01). This suggests that potassium produces vasodilation by the activation of vascular Na + ,K + -ATPase activity. Similarly, salt loading (180 mEq NaCl for 7 days) after treatment with diuretics could attenuate percent decrements of resistance with KCI infusions (39±3% versus 53±2%,p<0.01), whereas vascular resistance responses to sodium nitroprusside, a nonspecific vasodilator, and to verapamil, a calcium antagonist, did not change with salt loading after volume depletion. Therefore, salt loading could attenuate forearm vascular response to potassium specifically, as did the administration of ouabain. Evidence supports the hypothesis that volume expansion with salt loading increases endogenous ouabainlike Na + ,K + -ATPase inhibitor concentration, which plays a role in not only the control of extracellular fluid but also the regulation of vascular tone during salt loading. (Hypertension 1993^1:772-778)

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Section: Discussionsupporting

confidence: 73%

Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans.

Fujita

Ito

1993

Hypertension

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“…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.…”

Section: Effect Of Antagonists On Baseline Vascular Tonementioning

confidence: 66%

ATP‐induced vasodilation in human skeletal muscle

Ginneken

Meijer

Verkaik

et al. 2004

British J Pharmacology

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1 The purine nucleotide adenosine-5 0 -triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium-derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. 2 Adenosine 5 0 -triphosphate (0.2, 0.6, 6 and 20 nmol dl À1 forearm volume min À1 ) evoked a dosedependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 mg dl À1 min À1 , n ¼ 10), the blocker of Na þ /K þ -ATPase ouabain (0.2 mg dl À1 min À1 , n ¼ 8), the blocker of K Ca channels tetraethylammonium chloride (TEA, 0.1 mg dl À1 min À1 , n ¼ 10), nor by the K ATP -channel blocker glibenclamide (2 mg dl À1 min À1 , n ¼ 10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and L-NMMA (n ¼ 6) significantly increased the baseline forearm vascular resistance. The ATP-induced relative decreases in forearm vascular resistance were 4875, 6773, 8872, and 9272% in the absence and 2377, 6274, 8972, and 9371% in the presence of the combination of TEA, indomethacin and L-NMMA (Po0.05, repeated-measures ANOVA, n ¼ 6). A similar inhibition was obtained for sodium nitroprusside (SNP, Po0.05 repeated-measures ANOVA, n ¼ 6), indicating a nonspecific interaction due to the blocker-induced vasoconstriction. 3 ATP-induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and L-NMMA. Endothelium-independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies.

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“…In 10 separate experiments, ouabain (2.7 nmol/min) was infused for 15 minutes and blood flows were measured as described elsewhere. 21 Ouabain was continued for a further 3 minutes, coinfused with BaCl 2 (4 mol/min).…”

Section: Effects Of Bacl 2 and Ouabain On Basal Forearm Blood Flowmentioning

confidence: 99%

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

et al. 2002

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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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Effect of Local Infusion of Ouabain on Human Forearm Vascular Resistance and on Response to Potassium, Verapamil and Sodium Nitroprusside

Cited by 30 publications

References 0 publications

Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans.

Salt loads attenuate potassium-induced vasodilation of forearm vasculature in humans.

ATP‐induced vasodilation in human skeletal muscle

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

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