The role of vasopressin in essential hypertension. Plasma levels and effects of the V1 receptor antagonist OPC-21268 during different dietary sodium intakes.

To study the role of vasopressin (VP) in essential hypertension, we examined plasma levels of VP and blood pressure (BP) response to an orally active V1 receptor antagonist, OPC-21268, in hypertensive patients on diets with different sodium contents. Plasma VP was determined in 12 normotensive subjects and 12 patients with mild essential hypertension on a regular sodium diet, and in eight hypertensive patients on a high sodium (250 mmol/day) and a low sodium (25 mmol/day) diet. BP response was examined for 4 h after single oral administration of OPC-21268 (100 mg) or placebo in eight patients on the regular diet, and in six patients on the high and low sodium diets. In four patients on the regular diet, the effects of OPC-21268 on the baroreflex control of heart rate were also examined with intravenous injections of methoxamine. Plasma VP did not differ between the normotensive and hypertensive subjects. Levels of VP in the plasma was higher in the high sodium than in the low sodium period, but the difference was not significant. BP and heart rate did not change significantly after administration of OPC-21268 or placebo under either condition. OPC-21268 also failed to lower BP in salt-sensitive patients on the high sodium diet. The baroreceptor reflex sensitivity was not modified by the administration of OPC-21268. Our results suggest that VP does not play an important role in mild essential hypertension through its action on the V1 receptors regardless of dietary sodium intake.