Effects of a potassium-sparing/thiazide diuretic combination on cardiovascular reactivity to vasopressor agents

The vascular effects of a diuretic combination (spironolactone/altizide) were studied in 5 anuric patients undergoing dialysis by measuring changes in cardiovascular reactivity to norepinephrine (NE) and angiotensin II (AII) after infusion of incremental doses of these 2 vasopressor agents. There was a marked dose-response relation between NE and AII administration and mean (NE) or diastolic (AII) blood pressure (BP). Diuretic treatment moderated the increase in mean or diastolic BP induced by NE or AII. In addition, the pressor doses of NE and AII, which are also parameters of vascular reactivity, were significantly increased after diuretic treatment (NE, +101%; AII, +163%). Right atrial and pulmonary capillary wedge pressures increased along with BP in response to NE. Diuretic treatment also moderated the increase in right atrial and pulmonary capillary wedge pressures induced by NE. These results suggest that the antihypertensive action of spironolactone and altizide in combination is mainly due to a direct effect on resistance and capacitance vessels. The mechanisms by which diuretics modify the cardioreactivity remain poorly understood; however, they may modify electrolyte transport (sodium and calcium) across vascular smooth muscle cell membranes or stimulate prostaglandin release.