AT1 receptor blockade prevents the increase in blood pressure and the augmentation of intrarenal ANG II levels in hypertensive Cyp1a1-Ren2 transgenic rats fed with a high-salt diet.

摘要

INTRODUCTION: This study was performed to determine the effects of high-salt diet on the magnitude of the increases in systolic blood pressure (SBP) and kidney tissue angiotensin (ANG) II levels that occur after induction of ANG II-dependent malignant hypertension in Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)]. METHODS: Cyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days to induce ANG II-dependent malignant hypertension. RESULTS: Rats induced with I3C exhibited increases in SBP and elevations of ANG II levels in kidney cortex and medulla. In a second group of rats (n = 6), high-salt intake alone did not alter basal SBP; however, subsequent dietary administration of 0.3% I3C during continued high-salt intake elicited a substantially greater increase in SBP than observed in rats fed a normal salt diet. ANG II levels in kidney cortex and medulla of rats induced with I3C and fed a high-salt diet were elevated similarly to those in rats induced with I3C alone. Chronic administration of the AT1 receptor antagonist, losartan (100 mg/L in drinking water, n = 6), markedly attenuated the I3C-induced increase in SBP and prevented the augmentation of ANG II levels in kidney cortex and medulla in rats induced with I3C and maintained on a high-salt diet. CONCLUSIONS: Activation of AT1 receptors contributes to the augmented blood pressure and elevated kidney tissue ANG II levels that occur in Cyp1a1-Ren2 transgenic rats with malignant hypertension maintained on a high-salt diet.