Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats.

Abstract

To evaluate the role of the renin gene in the development of hypertension in Dahl salt-sensitive rats (SS/Jr/Hsd), we derived a congenic strain of rats homozygous for the salt-resistant renin allele (S/renrr) and compared them with a control strain homozygous for the salt-sensitive renin allele (S/ren(ss). Mean arterial pressure was significantly higher in 12-week-old S/renrr rats fed a high salt (8.0%) diet for 3 weeks than in S/ren(ss) rats or in SS/Jr/Hsd rats rederived from the foundation colony we used to generate the cogenic strain (195 +/- 3 [n = 49] versus 168 +/- 3 [n = 17] or 161 +/- 3 [n = 16] mm Hg). Mean arterial pressure was also higher in S/renrr rats than in S/ren(ss) rats raised from birth on either a very low salt (0.1%) diet (119 +/- 9 [n = 6] versus 100 +/- 7 [n = 7] mm Hg) or a low salt (0.4%) diet (143 +/- 1 [n = 22] versus 117 +/- 3 [n = 10] mm Hg). Plasma renin activity of S/renrr rats was significantly higher than that of S/ren(ss) rats fed a very low salt diet (5.7 +/- 2.0 versus 1.8 +/- 0.3) ng angiotensin l/mL per hour), a low salt diet (4.4 +/- 1.0 versus 1.1 +/- 0.3), or a high salt diet (1.5 +/- 0.2 versus 0.9 +/- 0.1). Urinary protein excretion was greater in S/renrr rats than in S/ren(ss) rats fed a high salt diet (244.2 +/- 48.5 versus 43.6 +/- 19.5 mg/24 h), and this was associated with significant reductions in renal blood flow (3.3 +/- 0.6 versus 4.6 +/- 0.5 mL/min per gram kidney weight) and glomerular filtration rate (0.49 +/- 0.11 versus 0.82 +/- 0.08 mL/min per gram kidney weight). Captopril (20 mg/kg i.v.) had no effect on blood pressure in S/ren(ss) rats fed a low salt diet, but it lowered blood pressure by 20 mm Hg in S/ren(rr) rats to the same level seen in untreated S/ren(ss) rats. Chronic administration of captopril (5 mg/100 mL drinking water) reduced blood pressure in S/renrr rats fed a high salt diet (170 +/- 5 mm Hg) to the same level seen in untreated S/ren(ss) rats, whereas it had no significant effect on blood pressure in S/ren(ss) rats. These results indicate that transfer of a salt-resistant renin allele to SS/Jr/Hsd rats raises plasma renin activity and augments the severity of hypertension and renal disease.