Benefits and side effects of blood pressure lowering treatment: what was wrong with doxazosin in the ALLHAT?
We studied the effect of various adrenergic components on vasopressin in groups of anephric rats. Pharmacological interventions included alpha 1-, alpha 2-, and beta-adrenergic receptor blockade and infusions of sodium nitroprusside to achieve a baseline blood pressure fall similar to that obtained by alpha 1-blockade, followed by hypertonic saline infusion to stimulate vasopressin release and administration of a specific V1 vascular vasopressin inhibitor to test the degree of blood pressure dependency on vasopressin. The combined hypotensive and osmolar stimuli of nitroprusside followed by hypertonic saline led to the highest level of plasma vasopressin (104 +/- 17 pg/ml, p less than 0.01) but only a 7 +/- 1 mm Hg fall in blood pressure in response to the vasopressin inhibitor. Rats subjected to alpha 1-blockade and saline infusion had the largest blood pressure reduction in response to the vasopressin inhibitor (43 +/- 5 mm Hg, p less than 0.001), despite a modest rise in vasopressin levels (18 +/- 2 pg/ml). Other pharmacological maneuvers produced intermediate responses in terms of vasopressin release and blood pressure response to the vasopressin inhibitor. There was no correlation between vasopressin levels achieved by each maneuver and the magnitude of blood pressure reduction in response to the vasopressin inhibitor. We conclude that 1) plasma levels of vasopressin under these conditions do not permit an accurate estimate of the magnitude of its pressor contribution to the maintenance of a given blood pressure level, which can be demonstrated only by the depressor response to a vasopressin inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)