Harrap S B, Doyle A E
J Hypertens Suppl. 1986 Oct;4(3):S249-52.
We have investigated the renal haemodynamics and sodium metabolism in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats during the first 10 weeks of life. Using constant infusion clearance measurements of 51Cr-EDTA and 125I-hippuran in unrestrained, conscious, 4-week-old rats we found a significant reduction in glomerular filtration rate (GFR) and renal blood flow (RBF), respectively, in SHR compared with WKY. The arterial blood pressure (BP) and renal vascular resistance were also significantly elevated in SHR at this age. Acute oral treatment with hydralazine increased SHR GFR and RBF to equal that of WKY, but acute angiotensin converting enzyme inhibition with oral MK 421 caused the GFR and RBF of SHR to exceed that of WKY. In addition, the plasma renin activity of 4-week-old SHR was significantly elevated compared with WKY. Total body sodium was measured from 1 to 10 weeks of age by determining the whole-body radioactivity of rats equilibrated on 22Na-labelled NaCl of constant specific activity. Indirect blood pressure and sodium intake were measured from weeks 4 to 10 inclusive. Relative sodium retention was observed in SHR both before and during the early developmental phase of hypertension. The sodium intake and BP of SHR were consistently higher than WKY throughout weeks 4 to 10. We propose that increased renal vascular resistance in immature SHR alters the pressure natriuresis relationship to cause sodium retention, with the subsequent development of hypertension.
我们研究了自发性高血压大鼠(SHR)和Wistar-Kyoto大鼠(WKY)在出生后前10周的肾脏血流动力学和钠代谢情况。通过对4周龄未束缚、清醒大鼠进行51Cr-EDTA和125I-马尿酸的恒速输注清除率测量,我们发现与WKY相比,SHR的肾小球滤过率(GFR)和肾血流量(RBF)分别显著降低。在这个年龄段,SHR的动脉血压(BP)和肾血管阻力也显著升高。用肼屈嗪进行急性口服治疗可使SHR的GFR和RBF增加至与WKY相当的水平,但用口服MK 421进行急性血管紧张素转换酶抑制会使SHR的GFR和RBF超过WKY。此外,4周龄SHR的血浆肾素活性与WKY相比显著升高。通过测定在恒定比活度的22Na标记氯化钠上平衡的大鼠全身放射性,从1至10周龄测量全身钠含量。从第4周直至第10周测量间接血压和钠摄入量。在高血压早期发育阶段之前及期间,SHR均观察到相对钠潴留。在第4周至第10周期间,SHR的钠摄入量和BP始终高于WKY。我们提出,未成熟SHR中肾血管阻力增加会改变压力-利钠关系,导致钠潴留,随后发展为高血压。