GLOMERULAR FUNCTION AND STRUCTURE IN THE SODIUM-REPLETE AND SODIUM-DEPLETE UNINEPHRECTOMIZED SPONTANEOUSLY HYPERTENSIVE RAT - EFFECT OF BLOOD-PRESSURE REDUCTION, GLOMERULAR STRUCTURE, AND BLOOD-PRESSURE REDUCTION

To assess the effects of chronic dietary sodium restriction and blood pressure reduction on glomerular function and structure during the pat hogenesis of hypertensive renal disease, experiments were conducted in uninephrectomized (UNX) spontaneously hypertensive rats (SHR) using t he dihydropyridine calcium antagonist manidipine. Male SHRs underwent UNX at age 10-11 weeks and subsequently were assigned to one of four g roups: sodium-replete (0.4%); sodium-replete and a predetermined antih ypertensive dose of manidipine (20 mg/kg body weight); sodium-deplete (0.09%); and sodium-deplete and manidipine (20 mg/kg body weight). Twe lve weeks later, renal morphologic and functional studies were perform ed. Sodium restriction had no significant effect on systolic blood pre ssure, but creatinine clearance and urinary protein excretion were dec reased, Importantly, mean glomerular volume and the prevalence of mesa ngial expansion were lower with sodium restriction. This occurred in t he presence of high concentrations of plasma and renal tissue angioten sin II. Manidipine significantly reduced systolic blood pressure in th e sodium-replete and sodium-deplete UNX-SHRs. This therapy was not ass ociated with significant changes in creatinine clearance and urinary p rotein excretion in the sodium-deplete or sodium-replete UNX-SHRs. The prevalence of mesangial expansion in the sodium-replete UNX-SHR was a pproximately 50% lower with manidipine. Plasma and renal tissue angiot ensin II concentrations were not affected by the drug. In the sodium-d eplete UNX-SHR, the prevalence of mesangial expansion was not reduced further by manidipine. However, plasma and renal tissue angiotensin II concentrations were increased significantly. Based on the results of this study, 1) in the sodium-replete UNX-SHR, the calcium antagonist m anidipine, given as effective antihypertensive therapy, attenuates ear ly glomerular injury without altering circulating or renal tissue angi otensin II; 2) sodium depletion, independent of blood pressure and sti mulation of circulating and renal tissue angiotensin II, attenuates ea rly glomerular injury after uninephrectomy; and 3) in sodium-deplete U NX-SHR, effective antihypertensive treatment with manidipine does not produce an additional reduction in early glomerular injury.