Jiang J, Stec D E, Drummond H, Simon J S, Koike G, Jacob H J, Roman R J
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Hypertension. 1997 Feb;29(2):619-27. doi: 10.1161/01.hyp.29.2.619.
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.
为评估肾素基因在 Dahl 盐敏感大鼠（SS/Jr/Hsd）高血压发生发展中的作用，我们培育了一种对盐耐受的肾素等位基因纯合的近交系大鼠（S/renrr），并将其与对盐敏感的肾素等位基因纯合的对照品系（S/ren(ss)）进行比较。给 12 周龄的 S/renrr 大鼠喂食高盐（8.0%）饮食 3 周后，其平均动脉压显著高于 S/ren(ss)大鼠或从我们用于培育近交系的基础群体中重新培育的 SS/Jr/Hsd 大鼠（195±3 [n = 49] 对 168±3 [n = 17] 或 161±3 [n = 16] mmHg）。从出生起就喂食极低盐（0.1%）饮食（119±9 [n = 6] 对 100±7 [n = 7] mmHg）或低盐（0.4%）饮食（143±1 [n = 22] 对 117±3 [n = 10] mmHg）的 S/renrr 大鼠，其平均动脉压也高于 S/ren(ss)大鼠。喂食极低盐饮食（5.7±2.0 对 1.8±0.3 ng 血管紧张素 I/mL 每小时）、低盐饮食（4.4±1.0 对 1.1±0.3）或高盐饮食（1.5±0.2 对 0.9±0.1）的 S/renrr 大鼠的血浆肾素活性显著高于 S/ren(ss)大鼠。喂食高盐饮食的 S/renrr 大鼠的尿蛋白排泄量高于 S/ren(ss)大鼠（244.2±48.5 对 43.6±19.5 mg/24 h），这与肾血流量（3.3±0.6 对 4.6±0.5 mL/min 每克肾重）和肾小球滤过率（0.49±0.11 对 0.82±0.08 mL/min 每克肾重）的显著降低有关。卡托普利（20 mg/kg 静脉注射）对喂食低盐饮食的 S/ren(ss)大鼠的血压没有影响，但它使 S/ren(rr)大鼠的血压降低了 20 mmHg，降至未治疗的 S/ren(ss)大鼠的水平。长期给予卡托普利（5 mg/100 mL 饮用水）可使喂食高盐饮食的 S/renrr 大鼠的血压（170±5 mmHg）降至未治疗的 S/ren(ss)大鼠的水平，而对 S/ren(ss)大鼠的血压没有显著影响。这些结果表明，将对盐耐受的肾素等位基因转移到 SS/Jr/Hsd 大鼠中会提高血浆肾素活性，并加剧高血压和肾脏疾病的严重程度。
