High salt intake exacerbates the magnitude of the increase in blood pressure in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension

Abstract

The present study was performed to determine the effects of high‐salt diet on the magnitude of the blood pressure increase that occurs following induction of ANG II‐dependent malignant hypertension in Cyp1a1‐Ren2 transgenic rats with inducible expression of the Ren2 renin gene [TGR(Cyp1a1Ren2)]. Cyp1a1‐Ren2 rats (n=6) were fed a normal diet containing 0.3% indole‐3‐carbinol (I3C) for 10 days to induce malignant hypertension. Rats induced with I3C exhibited an increase in systolic blood pressure (SBP) from 126±11 to 172±10 mmHg (P<0.001). In a second group (n=6), rats were fed a high salt diet (8% NaCl) for 7 days and then induced with 0.3% I3C for 10 days during continued high salt intake. High salt intake alone did not alter basal SBP (126±11 vs. 128±8 mmHg); however, subsequent dietary administration of 0.3% I3C during continued high salt intake increased SBP from 128±8 to 212 ±10 mmHg (P<0.001), a substantially greater increase in SBP than that observed in rats fed a normal salt diet (88±8 vs. 46±17 mmHg, P<0.001). Chronic administration of the AT1 receptor antagonist, Losartan (100 mg/L in drinking water, n=6), markedly attenuated the I3C‐induced increase in SBP (181±8 vs. 212±12 mmHg, P<0.01) in rats induced with I3C and maintained on a high salt diet. Thus, activation of AT1 receptors contributes to the exacerbation of malignant hypertension induced by high dietary salt intake in Cyp1a1‐Ren2 transgenic rats.