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 pathogenesis of hypertensive renal disease, experiments were conducted in uninephrectomized (UNX) spontaneously hypertensive rats (SHR) using the dihydropyridine calcium antagonist manidipine. Male SHRs underwent UNX at age 10-11 weeks and subsequently were assigned to one of four groups: sodium-replete (0.4%); sodium-replete and a predetermined antihypertensive dose of manidipine (20 mg/kg body weight); sodium-deplete (0.09%); and sodium-deplete and manidipine (20 mg/kg body weight). Twelve weeks later, renal morphologic and functional studies were performed. Sodium restriction had no significant effect on systolic blood pressure, but creatinine clearance and urinary protein excretion were decreased. Importantly, mean glomerular volume and the prevalence of mesangial expansion were lower with sodium restriction. This occurred in the presence of high concentrations of plasma and renal tissue angiotensin II. Manidipine significantly reduced systolic blood pressure in the sodium-replete and sodium-deplete UNX-SHRs. This therapy was not associated with significant changes in creatinine clearance and urinary protein excretion in the sodium-deplete or sodium-replete UNX-SHRs. The prevalence of mesangial expansion in the sodium-replete UNX-SHR was approximately 50% lower with manidipine. Plasma and renal tissue angiotensin II concentrations were not affected by the drug. In the sodium-deplete UNX-SHR, the prevalence of mesangial expansion was not reduced further by manidipine. However, plasma and renal tissue angiotensin II concentrations were increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Reams
G
G
Department of Medicine, University of Missouri.
Villareal
D
D
Wu
Z
Z
Luger
A
A
Knaus
J
J
Bauer
J
J
D000804:Angiotensin II / Q000032:analysis / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D004039:Diet, Sodium-Restricted; D004095:Dihydropyridines / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009392:Nephrectomy; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D012982:Sodium, Dietary; D000804:Angiotensin II; C054218:manidipine