Risk Factors for Glomerular Injury in Rats With Genetic Hypertension

Systemic and glomerular hypertension, hyperlipidemia, and massive proteinuria have been described as risk factors for the development of focal glomerulosclerosis (FGS). Previous studies have shown that Dahl salt-sensitive (S) rats with severe hypertension have elevated glomerular pressures and develop extensive FGS. In the present study, we determined whether Dahl S rats exhibit other risk factors for FGS. Dahl S rats were found to have elevated serum triglycerides at six weeks of age, compared to Dahl salt-resistant (R) rats. Between six and 24 weeks, systemic hypertension and progressive increases in both serum lipids and albuminuria occurred in Dahl S rats fed high salt (4% NaCl) chow. No changes in blood pressure or serum lipids occurred in Dahl R rats fed high salt. At 30 weeks, the incidence of FGS was 20 times greater in hypertensive Dahl S than in Dahl R. In a separate study, we compared risk factors for FGS in Dahl S rats and spontaneously hypertensive rats (SHR). The magnitude of glomerular capillary pressure, serum lipid levels, and urine albumin excretion were measured in male Dahl S rats and male SHR between 12 and 20 weeks of age. Normal values for the various parameters were established in a group of normotensive male Sprague-Dawley rats. For this study, all rats were fed standard chow containing 0.6% NaCl. Blood pressure was elevated (P < .01) in Dahl S (142 ± 2 mm Hg) and in SHR (173 ± 3 mm Hg) compared to the Sprague-Dawley rats (117 ± 3 mm Hg). Glomerular capillary pressure, however, was similar in all three groups. Serum cholesterol and urine albumin excretion were significantly elevated in Dahl S rats compared to the other two strains. Dahl S rats fed standard chow had 3.1 ± 0.6% of glomeruli with FGS at 15 to 20 weeks of age, whereas no FGS was seen in the other two strains. Thus, at an early age, Dahl S rats demonstrated two putative risk factors for FGS, namely, hyperlipidemia and albuminuria, which could have participated in the initiation of glomerular injury. Moreover, differences in risk factors other than the level of PGC might explain, in part, differences in the susceptibility to glomerular injury between Dahl S rats and SHR. Am J Hypertens 1989;2:9-13