Renal Functional Responses to Intrarenal Arterial Administration of the Direct Renin Inhibitor Aliskiren in Cyp1a1‐Ren2 Transgenic Rats with ANG II‐Dependent Malignant Hypertension

Abstract

The present study was performed to determine the effects of selective intrarenal administration of the direct renin inhibitor, aliskiren, on whole kidney hemodynamics and excretory function in Cyp1a1-Ren2 transgenic rats with ANG II-dependent malignant hypertension in the absence of the confounding influence of associated reductions in arterial blood pressure. Male Cyp1a1-Ren2 rats (n=5) were fed a normal diet containing indole-3-carbinol (0.3%, wt/wt) for 10 days to induce malignant hypertension. MAP and renal hemodynamics and excretory function were measured in pentobarbital-anesthetized rats during control conditions and following intrarenal administration of aliskiren (0.01 mg/kg). Intrarenal administration of aliskiren increased urine flow (10.47±1.7 to 12.96±2.6 μl/min, P<0.05) and urinary sodium excretion (0.46±0.15 to 1.16±0.26 μEq/min, P<0.05) without affecting MAP, GFR, or RPF. The present findings demonstrate that selective renal renin inhibition elicits diuretic and natriuretic effects in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. The data also indicate that de novo intrarenal ANG II generation may contribute to an augmented sodium reabsorptive capability and, thereby, to the elevated arterial blood pressure in ANG II-dependent malignant hypertension.