Studies on the role of endogenous sodium pump inhibitors in hypertension have used ouabain, a Na,K-ATPase inhibitor, as a pharmacological probe to test the effect of direct vascular Na,K-ATPase inhibition in man. Previous work has suggested that there are no alpha-adrenoceptor mediated components in the vasoconstrictor effect of this drug, although several animal and in vitro studies have shown a complex interaction between ouabain and either sympathetic neurotransmission or alpha-adrenergic excitation-contraction coupling mechanisms. To re-examine this issue, we infused ouabain at 7 micrograms/dl per min for 20 min without (saline infusion) or with phentolamine (8.0 micrograms/dl per min for 15 min), an alpha-adrenoceptor blocking agent, in uncomplicated mild to moderate hypertensive patients. The drugs were infused into the brachial artery, and forearm blood flow (by strain-gauge plethysmography), systemic blood pressure and heart rate were measured concomitantly. After local phentolamine pretreatment, ouabain lost its vasoconstrictor effect (n = 5). This result is unlikely to have been related to vasodilation because histamine, a non-alpha-adrenergic vasodilator, infused in another group (n = 5) of patients at rates roughly equieffective to phentolamine (0.05 microgram/dl per min for 15 min) did not modify the vasoconstrictor action of ouabain. Thus alpha-adrenoceptor mediated components caused the forearm vascular effect of ouabain and must be taken into account when using ouabain to study endogenous sodium pump inhibitor(s) in human hypertension.

Ouabain vasoconstricts human forearm arterioles through alpha-adrenergic stimulation.

TADDEI, STEFANO;SALVETTI, ANTONIO;PEDRINELLI, ROBERTO
1988

Abstract

Studies on the role of endogenous sodium pump inhibitors in hypertension have used ouabain, a Na,K-ATPase inhibitor, as a pharmacological probe to test the effect of direct vascular Na,K-ATPase inhibition in man. Previous work has suggested that there are no alpha-adrenoceptor mediated components in the vasoconstrictor effect of this drug, although several animal and in vitro studies have shown a complex interaction between ouabain and either sympathetic neurotransmission or alpha-adrenergic excitation-contraction coupling mechanisms. To re-examine this issue, we infused ouabain at 7 micrograms/dl per min for 20 min without (saline infusion) or with phentolamine (8.0 micrograms/dl per min for 15 min), an alpha-adrenoceptor blocking agent, in uncomplicated mild to moderate hypertensive patients. The drugs were infused into the brachial artery, and forearm blood flow (by strain-gauge plethysmography), systemic blood pressure and heart rate were measured concomitantly. After local phentolamine pretreatment, ouabain lost its vasoconstrictor effect (n = 5). This result is unlikely to have been related to vasodilation because histamine, a non-alpha-adrenergic vasodilator, infused in another group (n = 5) of patients at rates roughly equieffective to phentolamine (0.05 microgram/dl per min for 15 min) did not modify the vasoconstrictor action of ouabain. Thus alpha-adrenoceptor mediated components caused the forearm vascular effect of ouabain and must be taken into account when using ouabain to study endogenous sodium pump inhibitor(s) in human hypertension.
Taddei, Stefano; Salvetti, Antonio; Pedrinelli, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/204122
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