Vascular effects of loop diuretics: an in vivo and in vitro study in the rat

Abstract

The vascular effects of loop diuretics were studied in two models designed to eliminate hemodynamic repercussions linked to sodium and water depletion: in vivo, in unilaterally nephrectomized rats with a contralateral uretero-venous shunt, and in vitro, in the isolated perfused rat kidney. In anesthetized rats, local vascular resistance was calculated from the simultaneous recording of blood pressure and renal, iliac and carotid blood flows (electromagnetic flowmeter, Skalar). Furosemide and piretanide (10 to 80 mg/kg i.v.) induced a comparable dose-dependent decrease in renal vascular resistance, which was not modified by reserpine and indomethacin pre-treatment. The iliac relaxing response was blunted by vasoconstriction, which disappeared after combined treatment with reserpine and indomethacin. The relaxation induced in the iliac and carotid vasculature persisted after bilateral nephrectomy. In vitro, the vasorelaxing effect of diuretics in isolated rat kidneys perfused in an open circuit was studied after vascular tone had been re-established by a continuous perfusion of PGF2 alpha. Furosemide, piretanide and ozolinone induced a concentration-dependent decrease in renal tone (EC50 = 0.47 x 10(-4) mol/l, 1.03 x 10(-4) mol/l and 2.07 x 10(-4) mol/l respectively) in Wistar rats. A similar response to piretanide was found in spontaneously hypertensive stroke-prone rats (EC50 = 0.32 x 10(-4) mol/l) and in their normotensive controls (EC50 = 0.74 x 10(-4) mol/l). Our results show that loop diuretics induce a direct relaxation in the renal, iliac and carotid vasculature. This vascular effect, which appears at relatively high concentrations of the drugs, is prostaglandin independent and persists after bilateral nephrectomy.