Bagby S P, McDonald W J, Mass R D
Hypertension. 1979 Jul-Aug;1(4):347-54. doi: 10.1161/01.hyp.1.4.347.
To characterize the renin-angiotensin system in the Aoki-Okamoto spontaneously hypertensive rat (SHR) more fully, serial measurements of plasma renin activity (PRA), plasma renin concentration (PRC), renin reactivity (as relative index of circulating modifiers of the renin reaction) and renin substrate concentration were made in 6- to 64-week-old SHR and in age-matched Wistar-Kyoto normotensive rats (WKY). In the evolving phase of SHR hypertension (6 and 13 weeks of age), PRA was comparable to WKY control values, whereas mature SHR with established hypertension developed, between 13 and 35 weeks of age, a high-PRA state persisting through 64 weeks of age. In 64-week-old SHR, increased plasma volume (3.54 +/- 0.91 in SHR vs. 3.18 +/- 0.90 ml/100 g body weight in WKY, p less than 0.025), together with increased PRA (24.9 +/- 3.8 in SHR vs. 13.1 2.2 ng AI/ml plasma/hr in WKY, p less than 0.025), suggest that volume decrease cannot explain increased PRA. In 42-week-old SHR, PRA was incompletely suppressed by deoxycorticosterone acetate plus 1% saline orally for 4 days: 4.9 +/- 1.2 in SHR vs. 0.6 +/- 0.8 ng angiotensin I/ml plasma/hr in WKY, p less than 0.001. Modestly increased renin reactivity of plasma was observed in SHR at all ages studied, supporting the ubiquity of increased circulating accelerators (or decreased inhibitors) of the renin reaction in hypertensive states. However, elevated renin reactivity did not account for the transition from normal to high PRA observed in mature SHR, nor did renin substrate concentration, which was consistently lower in SHR than in age-matched WKY. Temporal patterns of, and strain differences in PRA were closely paralleled by variations in PRC but not by other reaction components. Significant elevation of serum creatinine in old SHR support the presence of renal injury. We conclude that PRA and PRC are normal in evolving SHR hypertension and progress to abnormally elevated levels after hypertension is established. We postulate that "high-renin" hypertension may develop as a consequence of the hypertensive state per se, perhaps due to nephrosclerotic vascular disease.
为了更全面地描述青木 - 冈本自发性高血压大鼠（SHR）中的肾素 - 血管紧张素系统，对6至64周龄的SHR和年龄匹配的Wistar - Kyoto正常血压大鼠（WKY）进行了血浆肾素活性（PRA）、血浆肾素浓度（PRC）、肾素反应性（作为肾素反应循环调节剂的相对指标）和肾素底物浓度的系列测量。在SHR高血压的发展阶段（6周和13周龄），PRA与WKY对照值相当，而患有已确立高血压的成熟SHR在13至35周龄之间出现了高PRA状态，并持续到64周龄。在64周龄的SHR中，血浆容量增加（SHR为3.54±0.91，而WKY为3.18±0.90 ml/100 g体重，p<0.025），同时PRA增加（SHR为24.9±3.8，而WKY为13.1±2.2 ng AI/ml血浆/小时，p<0.025），这表明容量减少不能解释PRA的增加。在42周龄的SHR中，口服醋酸脱氧皮质酮加1%盐水4天，PRA未被完全抑制：SHR为4.9±1.2，而WKY为0.6±0.8 ng血管紧张素I/ml血浆/小时，p<0.001。在所有研究年龄的SHR中均观察到血浆肾素反应性适度增加，这支持了高血压状态下肾素反应循环促进剂增加（或抑制剂减少）的普遍性。然而，肾素反应性升高并不能解释成熟SHR中从正常PRA到高PRA的转变，肾素底物浓度也不能解释，SHR中的肾素底物浓度始终低于年龄匹配的WKY。PRA的时间模式和品系差异与PRC的变化密切平行，但与其他反应成分无关。老年SHR血清肌酐的显著升高支持了肾损伤的存在。我们得出结论，在SHR高血压的发展过程中，PRA和PRC是正常的，在高血压确立后进展到异常升高的水平。我们推测“高肾素”高血压可能是高血压状态本身的结果，可能是由于肾硬化性血管疾病。
