INFLUENCE OF THE RENAL ENDOTHELIN SYSTEM ON THE AUTOREGULATION OF RENAL BLOOD-FLOW IN SPONTANEOUSLY HYPERTENSIVE RATS

The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investig ate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma re nin activity (PRA) and pressure natriuresis in spontaneously hypertens ive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehi cle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatab le suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA an d renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). F urthermore after bosentan the rats revealed a complete loss of RBF aut oregulation. In contrast no changes in autoregulation of CBF, pressure -dependent PRA and pressure natriuresis were observed. Our findings de monstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortic al vessels. These data suggest that the renal ET system plays an impor tant role in the dynamic regulation of renal blood flow in SHR.