Major role for ACE-independent intrarenal ANG II formation in type II diabetes.

摘要: Combination therapy of angiotensin-converting enzyme (ACE) inhibition and AT(1) receptor blockade has been shown to provide greater renoprotection than ACE inhibitor alone in human diabetic nephropathy, suggesting that ACE-independent pathways for ANG II formation are major significance disease progression. Studies were performed determine the magnitude intrarenal type diabetes. Although renal cortical protein activity [2.1 +/- 0.8 vs. 9.2 2.1 arbitrary fluorescence units (AFU) x mg(-1) min(-1)] intensity immunohistochemical staining significantly reduced ACE2 (16.7 3.2 7.2 2.4 AFU min(-1)) elevated, kidney I (113 24 110 45 fmol/g) (1,017 165 788 99 levels not different between control mice. Afferent arteriole vasoconstriction due conversion was similar kidneys (-28 3% at 1 microM) (-23 mice; a response completely inhibited by blockade. In kidneys, afferent produced attenuated inhibition, but serine protease inhibition. contrast, kidneys. conclusion, there is switch from ACE-dependent protease-dependent kidney. Pharmacological targeting these may further protection vascular disease.