DOSE-RELATED CARDIOVASCULAR EFFECTS OF SPIRONOLACTONE

The aim of this study was to assess the short-term hemodynamic effects of increasing doses of spironolactone (25, 50, and 75 mg/day) on oliguric patients (5 men, mean age 47 +/- 12 years) undergoing hemodialysis for chronic renal impairment. Parameters of interest included heart rate (HR), cardiac output, systemic vascular resistance (SVR), arterial pressure, right atrial pressure, and pulmonary capillary wedge pressure (PCWP). The study also evaluated how spironolactone modified the effects on arterial and right atrial pressures and PCWP of infusion of increasing doses of norepinephrine (20, 40, and 100 ng/kg/min) and angiotensin II (2,4, and 10 ng/kg/min). Compared with placebo, the lowest dose of spironolactone (25 mg/day) produced statistically significant (p < 0.05) modifications in systemic arterial pressures without a compensatory increase in cardiac output. The modifications were more pronounced at 50 and 75 mg/day, and the latter had a significant dose-dependent effect. Moreover, doses of 50 and 75 mg/day produced significant (p < 0.05) decreases in right atrial pressure and PCWP. Spironolactone administration caused the curve expressing the relation between an infused norepinephrine or angiotensin II dose and the blood pressure response to shift significantly (p < 0.05 to < 0.01) to the right, and the pressor doses of norepinephrine or angiotensin II showed a significant (p < 0.05 to < 0.01) dose-related increase, suggesting that treatment with spironolactone inhibited cardiovascular reactivity. This effect was observed on both the capacitance (i.e., low-pressure) and resistance (i.e., high pressure) vessels. Thus, an important dose-related effect of spironolactone on both the high- and low-pressure systems appears to play a major role in the drug's vascular and antihypertensive effects.