Enhanced Urinary Angiotensinogen Excretion in Cyp1a1‐Ren2 Transgenic Rats with Inducible ANG II‐Dependent Malignant Hypertension

Abstract

The present study was performed to determine if urinary angiotensinogen excretion is increased in Cyp1a1‐Ren2 transgenic rats [strain name: TGR(Cyp1aRen2)] with inducible ANG II‐dependent malignant hypertension. Adult male 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. Rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (208±7 vs. 127±3 mmHg, P<0.001), marked proteinuria (29.4±3.6 vs. 5.0±0.4 mg/day, P<0.01), and augmented urinary angiotensinogen excretion (996±186 vs. 199±19 mg/day, P<0.05). Chronic administration of the AT1 receptor antagonist, candesartan (25 mg/L in drinking water, n=6), prevented the I3C‐induced increases in SBP (125±5, P<0.001), proteinuria (7.3±1.5 mg/day, p<0.001) and urinary angiotensinogen excretion (488±51 mg/day, P<0.05). The present findings confirm that AT1 receptor activation contributes to the increase in SBP and proteinuria in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension. These data also demonstrate that the urinary excretion of angiotensinogen is markedly augmented in ANG II‐dependent malignant hypertension. Such increased urinary angiotensinogen excretion likely reflects an AT1 receptor‐mediated stimulation of intrarenal angiotensinogen production which may contribute to augmented intrarenal ANG II levels and, thereby, to the increased blood pressure in Cyp1a1‐Ren2 transgenic rats with inducible ANG II‐dependent malignant hypertension.