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. This finding is not characteristic of hypertensive renal dysfunction and suggests that the mouse renin transgene can affect the kidney through mechanisms that do not solely depend on the presence of hypertension.