Variation of Plasma and Kidney Renin Activities Among Substrains of Spontaneously Hypertensive Rats

Abstract

Plasma and kidney renin activity (PRA, KRA) were determined in the spontaneously hypertensive (SHR) rats, the stroke-resistant and -prone substrains (SHRSR, SHRSP) from 5 to 30 weeks of age. Results were compared with those of two normotensive strains, Wistar-Kyoto (WKY) and Donryu (DON) rats. PRA in the SHRSP at 20 and 30 weeks of age were significantly increased when compared to other strains of rats (P < 0.01). In SHRSP rats at these ages, blood pressure exceeded the critical level of 220 mmHg and cerebral lesions were observed in 41% at autopsy. There were no significant differences in PRA among other hypertensive and normotensive strains. KRA in three substrains of the SHR were normal or subnormal as compared to WKY and DON rats. These results indicate that a direct role of the renin-angiotensin system in the SHR and its substrains can be excluded in the initiation and the maintenance of hypertension. However, the activated renin-angiotensin system in SHRSP rats in the course of malignant hypertension at 20 weeks of age and later, could participate in raising blood pressure above the levels of the SHR and SHRSR. Considering out data and others, there are many similarities in renin profile between the SHR and its two substrains, and human essential hypertension in which PRA can be classified as low, normal or high.

A new potent inhibitor of converting enzyme: (2R,4R)-2-(2-hydroxyphenyl)-3-(3-mercaptopropionyl)-4-thiazolidinecarboxylic acid(SA446).

“…However, the compound also reduced blood pressure in spontaneously hypertensive rats, though higher doses were required. Since plasma renin activity of adult spontaneously hyper tensive rats shows no difference or is lower than levels in normotensive adult rats (15), mechanisms other than renin-angiotensin system may be involved in the hypotensive effects of SA446. It has been reported that kininase II is identical with converting enzyme and the affinity of BK for the enzyme is greater than that of Al (10).…”

Antihypertensive Effect of Chronic KT3-671, a Structurally New Nonpeptide Angiotensin AT1-Receptor Antagonist, in Stroke-Prone Spontaneously Hypertensive Rats

“…In the present study, we investigated the effects of repeated oral administration of KT3-671 for 7 weeks on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery in 15-week-old stroke-prone spontaneously hypertensive (SHRSP) rats (8), a hypertensive model with high plasma renin activity (9,10).…”

“…Systolic blood pressure and heart rate were determined without anesthesia (12,13). In the sixth week of the experiment, after determination of renal function and blood pressure by the tail-cuff method, a catheter was inserted into the abdominal aorta through the femoral artery under anesthesia with sodium pentobarbital (9). The rats were allowed to recover from surgery for one week, and daily drug administration was continued during the recovery period.…”

“…PRC was determined by the method of Carvalho et al (14) with some modifications (9). Briefly, sample plasma was incubated with the plasma renin substrate pool obtained from 24-hr-nephrectomized rats in the presence of inhibitors of angiotensinase and converting enzyme.…”

Effects of Enalapril and Captopril on Urinary Excretion of Kinins and Electrolytes in Stroke-Prone Spontaneously Hypertensive Rats

“…To investigate the possible involvement of renal kinins in the antihypertensive effect of CE inhibitors, we determined the urinary excretion of kinins and electrolytes in stroke-prone spontaneously hypertensive (SHRSP) rats during treatment with enalapril and captopril. We have previously demonstrated that plasma renin activity in SHRSP rats is elevated during the late developmental and maintenance stage of hypertension (7,8) and that CE inhibitors produce a marked antihypertensive effect and prevent development of malignant hyper tensive cardiovascular diseases in this hyper tensive model (9,10).…”