Renal function in hypertensive rats transgenic for mouse renin gene.
The recent development of a transgenic rat strain carrying the mouse ren-2 renin gene [TGR(mRen2)27] has provided a new model of hypertension characterized by suppressed plasma renin levels and marked hyperproreninemia. In this long-term study, we examined the kidney function of these animals. Transgenic rats had significantly (P < 0.01) higher blood pressures than control animals at 2, 4, and 8 mo of age. However, the severity of their hypertension diminished over time (225 +/- 8 mmHg at age 2 mo vs. 169 +/- 5 mmHg at age 8 mo, P < 0.001), indicating age-dependent transgene regulation. Whole kidney and single-nephron blood flows and glomerular filtration rates did not differ between control and TGR(mRen2)27 animals studied with micropuncture techniques at 4 and 8 mo of age. Preglomerular vasoconstriction was responsible for this normal autoregulatory response. Elevated preglomerular vascular resistance of transgenic rats prevented transmission of systemic hypertension to glomeruli at 4 but not 8 mo of age leading to increased glomerular capillary pressures in these older animals (53 +/- 1 vs. 48 +/- 1 mmHg, P < 0.05). Pathological albuminuria appeared as early as 2 mo of age but did not increase over the subsequent 6 mo of follow-up. The incidence of glomerulosclerosis, assessed at 4 and 8 mo of age, was greater in TGR(mRen2)27 than control animals (6.6 +/- 1.4% vs. 0.9 +/- 0.3%, P = 0.01) but did not differ between 4- and 8-mo-old transgenic rats. Glomerular ultrafiltration coefficients were significantly elevated (P < 0.05) in transgenic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Springate
J E
JE
Department of Pediatrics, State University of New York at Buffalo School of Medicine and Biomedical Sciences.
Feld
L G
LG
Ganten
D
D
D000818:Animals; D030801:Animals, Genetically Modified; D001794:Blood Pressure; D001835:Body Weight; D005919:Glomerular Filtration Rate; D006400:Hematocrit; D006579:Heterozygote; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009399:Nephrons / Q000502:physiology / Q000503:physiopathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012079:Renal Circulation; D012083:Renin / Q000096:biosynthesis / Q000235:genetics*; D014655:Vascular Resistance
D012083:Renin