Acute effects of bezafibrate on blood pressure and renal haemodynamics in SHR and WKY rats.

Abstract

Bezafibrate, a fibric acid analogue, has well-established lipid- and fibrinogen-lowering properties. Some data exist pointing towards a blood-pressure-lowering effect of bezafibrate. Thus the aim of this study was to examine the acute effect of bezafibrate on blood pressure and renal haemodynamics in hypertensive and normotensive rats. 8 Wistar-Kyoto (WKY) and 12 spontaneously hypertensive rats (SHR) 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 flow (RBF), cortical blood flow (CBF), and medullary blood flow (MBF) were monitored continuously, together with plasma renin activity (PRA), urine volume and urinary Na+, K+, and protein concentration (15-min intervals). Bezafibrate reduced MAP in a dose-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 vehicle, 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 increase in RBF was paralleled by an increase in CBF. No effect of bezafibrate on MBF, PRA, urine flow, or urinary Na+, K+ or protein excretion was observed. The observed effects could not be attributed to one of the classic vasodilating mechanisms. We conclude that in rats bezafibrate is a potent hypotensive drug exhibiting additional effects on renal haemodynamics.