Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats
Transfer of a salt-resistant renin allele raises blood pressure in Dahl salt-sensitive rats
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DOI：
10.1161/01.hyp.29.2.619
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发表时间：
1997-02-01
期刊：
影响因子：
8.3
通讯作者：
Roman, RJ
中科院分区：
文献类型：
--
作者：
Jiang, J;Stec, DE;Roman, RJ
为了评估肾素基因在Dahl盐敏感大鼠（SS/Jr/Hsd）高血压发生中的作用，我们获得了一个盐敏感性肾素等位基因纯合子（S/ren（ss））的大鼠同源品系，并将其与盐敏感性肾素等位基因纯合子（S/ren（ss））的对照品系进行了比较。喂食高盐（8.0%）饮食3周的12周龄S/ren（ss）大鼠的平均动脉压显著高于S/ren（ss）大鼠或从我们用于产生同类品系的基础群体再衍生的SS/Jr/Hsd大鼠（195+/-3（n=49）vs 168+/-3（n=17）或161+/-3（n=16）mmHg。S/ren（ss）大鼠的平均动脉压也高于从出生起接受极低盐（0.1%）饮食（119+/-9 [n=6] vs 100+/-7 [n=4] mm Hg）或低盐（0.4%）饮食（143+/-1 [n=22] vs 117+/-3 [n=10] mm Hg）饲养的S/ren（ss）大鼠。S/ren（ss）大鼠的血浆肾素活性显著高于喂食极低盐饮食（5.7+/-2.0 vs 1.8+/-0.3 ng血管紧张素I/mL/小时）、低盐饮食（4.4+/-1.0 vs 1.1+/-0.3）或高盐饮食（1.5+/-0.2 vs 0.9+/-0.1）的S/ren（ss）大鼠。S/ren（ss）大鼠的尿蛋白排泄量大于喂食高盐饮食的S/ren（ss）大鼠（244.2 ± 48.5 vs 43.6 ± 19.5 mg/24 h），这与肾血流量的显著减少有关（3.3+/-0.6 vs 4.6+/-0.5 mL/min/g肾重）和肾小球滤过率（0.49+/-0.11 vs 0.82+/-0.08 mL/min/g肾重）。卡托普利（20 mg/kg IV）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（ss）大鼠的血压降低了20 mm Hg，与未治疗的S/ren（ss）大鼠相同。长期给予巯甲丙脯酸（5 mg/100 mL饮用水）可使喂食高盐饮食（170+/-5 mm Hg）的S/ren（ss）大鼠的血压降低至与未治疗的S/ren（ss）大鼠相同的水平，但对S/ren（ss）大鼠的血压无显著影响。这些结果表明，耐盐的肾素等位基因转移到SS/Jr/Hsd大鼠提高血浆肾素活性，增加高血压和肾脏疾病的严重程度。
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(ss)) 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(ss) 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(ss) 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(ss) 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(ss) 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(ss) 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(ss) 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.