RENAL ALTERATIONS IN L-NAME HYPERTENSION - INFLUENCE OF LOSARTAN AND BOSENTAN

The influence of losartan and the endothelin A and B receptor antagoni st, bosentan was assessed on the alterations in renal hemodynamic and function as well as urinary albumin excretion (taken as an index of re nal lesions) associated with L-NAME hypertension. L-NAME was given for 4 weeks (20 mg/100 mL in the drinking (fluid) followed by a 2-week pe riod of concomitant treatment with L-NAME and losartan or bosentan (30 and 30 mg/kg, gavage), A group of rats received L-NAME without additi onal treatment and a group of rats were not given L-NAME and served as normotensive controls. Systolic arterial pressure (SAP) was measured before L-NAME, and before and every 5 days of losartan or bosentan tre atment period, Urinary excretion of albumin (UAlb) was determined befo re and at the end of treatment period. Under anesthesia, glomerular fi ltration rate (GFR) and renal plasma flow (RPF) were estimated by the clearance method and the filtration fraction was calculated [FF = 100 (GFWRPF)]. [GRAPHICS] The rise in arterial pressure as well as the re duction in GFR and RPF associated with L-NAME hypertension were marked ly blunted by losartan. In contrast, bosentan did not affect GFR but p artially restored RPF, an effect accompanied by a fall in FF. In addit ion, the rise in UAlb induced by L-NAME was normalized by losartan and attenuated by bosentan. The present findings indicate that angiotensi n II has a major role in the maintenance of L-NAME hypertension and su ggest that endothelin may mediate the renal alterations independently of a blood pressure lowering effect.