ACUTE EFFECTS OF ANGIOTENSIN-II RECEPTOR ANTAGONIST ON AUTOREGULATIONOF ZONAL GLOMERULAR-FILTRATION RATE IN RENOVASCULAR HYPERTENSIVE RATS

This study was designed to assess the renal capability to autoregulate total blood flow, glomerular filtration rate (GFR) and local GFR in o uter, middle and inner cortical layers (OC, MC, IC:) in the two-kidney , one-clip (2K-1C) renovascular hypertensive rat, with or without acut e infusion of the angiotensin II receptor antagonist losartan (5 mg/kg , i.v.). Age-matched, sham-operated Wistar rats were used as controls. The hemodynamic study in all animals was performed 4 weeks after clip ping. The clipping increased blood pressure significantly, whereas los artan reduced the renal arterial pressure (RAP) from 165+/-s to 125+/- 6 mm Hg (p<0.01) in 2K-1C hypertensive rats and reduced the RAP from 1 07+/-2 to 101+/-1 mm Hg (p<0.05) in normotensive animals. Renal blood flow (RBF), total and local GFR were decreased in the nonclipped kidne y of 2K-1C hypertensive rats compared with sham-operated rats, but los artan significantly increased the RBF and GFR. RBF was well maintained in response to reduction in RAP in the nonclipped kidneys with and wi thout losartan treatment. The capability of total GFR autoregulation w as impaired in untreated 2K-1C hypertensive rats and losartan-treated sham-operated rats, whereas losartan completely abolished GFR autoregu lation in the nonclipped kidney of 2K-1C hypertensive rats. Losartan i mpaired autoregulation of zonal GFR to the same extent in all three co rtical layers of sham-operated rats, whereas in the nonclipped kidney of 2K-1C hypertensive rats losartan had a more pronounced effect on th e superficial GFR autoregulation than in middle and inner cortex, indi cating that angiotensin II plays a major role in regulating the GFR re sponse to the acute changes of renal arterial pressure.