Hypertension
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Clinical Trial Controlled Clinical Trial
Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients.
We assessed the clinical and pharmacological profile of the orally active V(1) vascular vasopressin (AVP) receptor nonpeptide antagonist SR49059 (SR) during the osmotic stimulation of AVP release in hypertensive patients. In a double-blind crossover-versus-placebo study, 24 untreated stage I or II essential hypertensive patients (12 whites and 12 blacks) received a single 300 mg oral dose of SR 2 hours before the stimulation of AVP secretion with a 5% hypertonic saline infusion. Hemodynamic, humoral, and hormonal parameters were monitored for up to 28 hours after drug administration. ⋯ SR effects were similar in the 2 ethnic groups as well as in salt-sensitive versus salt-resistant patients. In a situation of AVP osmotic release and volume expansion in hypertensive patients, a single oral dose of the V(1) vascular AVP receptor nonpeptide antagonist SR49059, which is able to block AVP-induced platelet aggregation, exerts a transient vasodilation effect that is not associated with a sustained blood pressure reduction. SR49059 is a pure V(1) vascular receptor antagonist that is devoid of V(2) renal receptor actions.