Renal functional responses to selective intrarenal renin inhibition in Cyplal-Ren2 transgenic rats with ANG Il-dependent malignant hypertension

摘要

Angiotensin (ANG) Il-dependent hypertension is characterized by increases in intrarenal ANG II levels, derangement in renal hemodynamics, and augmented tubular sodium reabsorptive capability. Increased nephron expression of renin-angio-tensin system components, such as angiotensinogen by proximal tubule cells and renin by collecting duct principal cells, has been associated with an augmented ability of the kidney to form ANG II in hypertensive states. However, the contribution of de novo intrarenal ANG II production to the development and maintenance of ANG Il-dependent hypertension remains unclear. The present study was performed to determine the effects of selective intrarenal renin inhibition on whole kidney hemodynamics and renal excretory function in Cyplal-Ren2 rats with ANG Il-dependent malignant hypertension in the absence of the confounding influence of associated reductions in mean arterial pressure (MAP). Male Cyplal-Ren2 transgenic rats were induced to develop malignant hypertension, anesthetized, and surgically prepared for intrarenal administration of the direct renin inhibitor aliskiren (0.01 mg/kg).