ACUTE EFFECTS OF BEZAFIBRATE ON BLOOD-PRESSURE AND RENAL HEMODYNAMICSIN SHR AND WKY RATS

Background. Bezafibrate, a fibric acid analogue, has well-established lipid-and fibrinogen-lowering properties. Some data exist pointing tow ards a blood-pressure-lowering effect of bezafibrate. Thus the aim of this study was to examine the acute effect of bezafibrate on blood pre ssure and renal haemodynamics in hypertensive and normotensive rats. M ethods. 8 Wistar-Kyoto (WKY) and 12 spontaneously hypertensive rats (S HR) were treated with i.v. bolus injections of vehicle and 1-10 mg of bezafibrate in increasing doses every 15 min. Mean arterial pressure ( MAP), renal blood how (RBF), cortical blood flow (CBF), and medullary blood flow (MBF) were monitored continuously, together with plasma ren in activity (PRA), urine volume and urinary Na+, K+, and protein conce ntration (15-min intervals). Results. Bezafibrate reduced MAP in a dos e-dependent manner (mean +/- SEM): in WKY, 1 mg bezafibrate, -1.13 +/- 0.61 mmHg and after 10 mg bezafibrate, -7.25 +/- 1.10 mmHg; in SHR, - 0.60 +/- 0.43 and -5.83 +/- 0.90 mmHg respectively. In contrast to veh icle, bezafibrate induced a dose-dependent increase in RBF (WKY, 0.21 +/- 0.10 and 0.83 +/- 0.48 ml/min;; SHR, 0.38 +/- 0.10 and 3.09 +/- 0. 45 ml/min respectively) and a corresponding decrease in renal vascular resistance which was significantly greater in SHR than in WKY. The in crease in RBF was paralleled by an increase in CBF. No effect of bezaf ibrate on MBF, PRA, urine flow, or urinary Na+, K+ or protein excretio n was observed. The observed effects could not be attributed to one of the classic vasodilating mechanisms. Conclusions. We conclude that in rats bezafibrate is a potent hypotensive drug exhibiting additional e ffects on renal haemodynamics.