Sympathetic vasoconstriction as a mechanism of action of ouabain in forearm arterioles of hypertensive patients.
1. The interaction of ouabain, a Na+/K+ adenosine 5'-triphosphatase inhibitor, with sympathetic mechanisms of vasoconstriction, as well as its possible site(s) of action, were investigated in forearm arterioles of patients with uncomplicated hypertension. 2. Intra-arterial infusion of ouabain per se decreased forearm blood flow without changes in systemic arterial pressure or contralateral flow. However, the vasoconstrictor effect of the glycoside was abolished after local pretreatment with either phentolamine, a competitive alpha-adrenoceptor antagonist, or bretylium tosylate, a neurotransmitter blocker. 3. To exclude a non-specific effect due to the vasodilatation, a similar protocol was performed using histamine, which acts independently of sympathetic mechanisms. The vascular effect of ouabain was maintained in spite of histamine-induced increases in forearm blood flow even greater than those obtained from either blocker. 4. To discriminate between pre- and post-synaptic site(s) of action of ouabain, exogenous noradrenaline was infused intra-arterially after inactivation of local neurotransmitter release by bretylium, thus causing direct postsynaptic vascular alpha-adrenoceptor stimulation. Under these conditions, noradrenaline decreased forearm blood flow irrespective of the presence or absence of ouabain. 5. Thus, local sympatholysis by drugs acting on different levels of the sympathetic neuroeffector junction abolished the effect of ouabain, whereas histamine did not influence it. The data provide positive evidence for an effect of ouabain on sympathetically mediated vasoconstriction. This action is apparently not exerted at a postsynaptic site but possibly by enhancing neurotransmitter release. 6. If a circulating endogenous ouabain-like Na+/K+ adenosine 5'-triphosphatase inhibitor is relevant to the development of hypertension in man, it might act through a similar mechanism.
Pedrinelli
R
R
Hypertension Unit, I Clinica Medica, University of Pisa, Italy.
Taddei
S
S
Salvetti
A
A
D001160:Arterioles / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects
D013566:Sympathomimetics; D014662:Vasoconstrictor Agents; D010042:Ouabain