Serial renin-angiotensin studies in spontaneously hypertensive and wistar-kyoto normotensive rats: Transition from normal-to high-renin status during the established phase of spontaneous hypertension

To characterize the renln-angiotensin system in the Aokl-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 < 0.025), together with increased PRA (24.9 ± 3.8 in SHR vs. 13.1 2.2 ng Al/ml plasma/hr in WKY.p < 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 < 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 "higb-renin" hypertension may develop as a consequence of the hypertensive state perse, perhaps due to nepbrosclerotic vascular disease.