Enhanced renal response to intracerebroventricular angiotensins II and III in spontaneously hypertensive rats

Abstract

The acute effects of intracerebroventricular (i.c.v.) administration of angiotensin III (ANG III) on blood pressure (BP) and renal function were investigated in spontaneously hypertensive rats (SHR, n = 31) and Wistar-Kyoto (WKY) normotensive rats (n = 6). ANG II was also administered to the same rats for comparison of its renal effect. BP and renal clearance responses were measured before and during ANG injections. The results showed that i.c.v. injections of 1, 5 and 50 pmol of ANG III did not significantly alter BP in SHR, but a high dose of ANG III (50 pmol) caused a vasopressor effect (7 +/- 4 mmHg) in WKY rats. There were significant increases in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow, absolute and fractional excretions of sodium and potassium, osmolar clearance and free water reabsorption rate following i.c.v. administration of ANG III in both SHR and WKY rats. However, the enhancement in renal responsiveness to ANG III was greater in SHR than in the WKY group. At 5 pmol of ANG III, the peak increases in GFR (96 +/- 23%), diuresis (316 +/- 102%) and natriuresis (712 +/- 281%) in SHR were significantly greater than those in WKY rats (40 +/- 13%, 152 +/- 89%, 229 +/- 130%, resp.). The renal effect of central ANG III was blocked by i.c.v. ANG III antagonist, [Ile7]-ANG III, but was enhanced by bestatin, an ANG III metabolic enzyme inhibitor. I.c.v. administration of ANG II at 50 pmol increased BP in both SHR and WKY rats (14 +/- 3 and 10 +/- 3 mmHg, resp.). Greater diuretic and natriuretic responses to ANG II were also noted in SHR than in WKY rats. These results indicate that central ANG III is as active as ANG II in modulating renal function. Furthermore, the enhanced renal response to i.c.v. ANGs II and III in SHR suggests a hyperactive central RAS implicated in BP and body fluid regulation in this genetic hypertensive strain.