Enalapril and renal function in hypertensive rats transgenic for mouse renin gene.
We examined the effect of long-term enalapril treatment on renal function and histology in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated transgenic rats had significantly (P<.01) higher blood pressures than treated transgenic and control animals throughout the study. Urinary nitric oxide metabolite excretion was significantly lower in young transgenic rats and rose with enalapril, suggesting abnormal TGR nitric oxide production and its correction by enalapril. Converting enzyme inhibition produced preferential preglomerular vasodilatation and increased renal blood flow (6.5 +/- 0.5 versus 9.0 +/- 0.7 mL/min per gram kidney weight, P<.05) without altering whole-kidney and single-nephron glomerular filtration rates in TGR(mRen2)27. Glomerular capillary pressure fell modestly in treated transgenic animals (54 +/- 1 versus 50 +/- 1 mm Hg, P<.05). These hemodynamic changes were associated with reductions in albuminuria (59 +/- 6 versus 9 +/- 2 mg/d, P<.01) and glomerulosclerosis in TGR. However, urinary albumin excretion (15 +/- 3 versus 3 +/- 1 mg/d, P<.05) and glomerulosclerosis also declined in treated control animals in the absence of significant alterations in glomerular hemodynamics. The mechanism of the beneficial effect of enalapril on the TGR(mRen2)27 kidney is unclear but could involve either control of hypertension or suppression of the intrarenal renin-angiotensin system.
Springate
J E
JE
Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo Veterans Affairs Medical Center, USA.
Feld
L G
LG
Ganten
D
D
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology*; D006439:Hemodynamics; D006973:Hypertension / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000097:blood / Q000235:genetics* / Q000652:urine; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*
D004656:Enalapril; D012083:Renin