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/ren rr ) 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/ren rr 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 congenic 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/ren rr 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=4] 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/ren rr 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 I/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/ren rr 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 IV) 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/ren rr 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.