VASCULAR EFFECTS OF LOOP DIURETICS - AN IN-VIVO AND IN-VITRO STUDY INTHE RAT

The vascular effects of loop diuretics were studied in two models desi gned to eliminate hemodynamic repercussions linked to sodium and water depletion: in vivo, in unilaterally nephrectomized rats with a contra lateral uretero-venous shunt, and in vitro, in the isolated perfused r at kidney. In anesthetized rats, local vascular resistance was calcula ted from the simultaneous recording of blood pressure and renal, iliac and carotid blood flows (electromagnetic flowmeter, Skalar). Furosemi de and piretanide (10 to 80 mg/kg i. v.) induced a comparable dose-dep endent decrease in renal vascular resistance, which was not modified b y reserpine and indomethacin pre-treatment. The iliac relaxing respons e was blunted by vasoconstriction, which disappeared after combined tr eatment 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 PGF(2 alpha). Furosemide, piretanide and ozolinone induced a concentration-dependent decrease in renal tone (EC(50) = 0.47 x 10(-4) mol/l, 1.03 x 10(-4) mol/l and 2.0 7 x 10(-4) mol/l respectively) in Wistar rats. A similar response to p iretanide was found in spontaneously hypertensive stroke-prone rats (E C(50), = 0.32 x 10(-4) mol/l) and in their normotensive controls (EC(5 0) = 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 t he drugs, is prostaglandin independent and persists after bilateral ne phrectomy.