Ouabain vasoconstricts human forearm arterioles through alpha-adrenergic stimulation.
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
S
S
Hypertension Unit, University of Pisa, Italy.
Salvetti
A
A
Pedrinelli
R
R
D000328:Adult; D001132:Arm / Q000098:blood supply; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D010042:Ouabain; D006632:Histamine; D010646:Phentolamine