Effect of indapamide on phosphate metabolism and vascular reactivity

The effect of indapamide, a nonthiazide diuretic, on urinary electrolytes, renal hemodynamics, and tissue inorganic phosphate was examined in normal anesthetized rats, as well as on vascular reactivity in vitro. Intravenous injections of 0.5 ml/kg of 1 x 10(-5), 1 x 10(-4), and 1 x 10(-3) M indapamide solutions reduced mean arterial pressure from 123 to 114, 130 to 113, and 128 to 114 mm Hg and the plasma phosphate concentrations from 6.4 to 4.2, 6.6 to 4.8, and 7.0 to 4.5 mg/dl, respectively. Similarly, there was a dose-dependent effect of indapamide on fractional excretion of phosphate, which increased from 17 to 44, 24 to 53, and 18 to 75 percent in animals receiving increasing doses of indapamide. This effect of indapamide on the external phosphate balance was associated with significant reduction of kidney cortex and skeletal muscle total inorganic phosphate. In contrast, fractional sodium excretion augmented by 2.6, 2.5, and 2.5 percent, respectively, at each dose of indapamide. This compound also reduced significantly the contractions of strips of rabbit aorta and mesenteric artery elicited by norepinephrine (0.01 to 1.0 micrograms/ml). These results suggest that indapamide-induced reduction of blood pressure could be mediated by an effect of this drug on phosphate balance, and probably on vascular reactivity.