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(Hypertension. 1997;29:619-627.)
© 1997 American Heart Association, Inc.
Articles |
Transfer of a Salt-Resistant Renin Allele Raises Blood Pressure in Dahl Salt-Sensitive Rats
the Department of Physiology and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, and Cardiovascular Research Center, Massachusetts General Hospital, Charlestown (J.S.S.).
Correspondence to Dr Richard J. Roman, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
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/renss). 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/renss 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/renrr rats than in S/renss 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/renrr rats was significantly higher than that of S/renss 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/renrr rats than in S/renss 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/renss rats fed a low salt diet, but it lowered blood pressure by 20 mm Hg in S/renrr rats to the same level seen in untreated S/renss 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/renss rats, whereas it had no significant effect on blood pressure in S/renss 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.
Key Words: congenic strain • renin gene • genotype • phenotype • hypertension • renal function
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