The Molecular Basis of Increased Glomerulosclerosis after Blockade of the Renin Angiotensin System in Growth Hormone Transgenic Mice

摘要: Abstract BACKGROUND: Angiotensin converting enzyme inhibitor (ACEi) therapy delays the onset of renal failure in diabetic nephropathy and inhibits or proteinuria several animal models. MATERIALS AND METHODS: We examined this question using a transgenic model chronic glomerulosclerosis caused by an excess production growth hormone (GH) which there is progressive glomerular scarring leading to uremia. In addition, since GH mice do not have systemic hypertension elevated filtration rate, we could address whether ACEi angiotensin II receptor antagonists (AII RA) had effect on development under these conditions. Since matrix accumulates because alterations balance between its synthesis degradation, AII RA parameters. RESULTS: Systemic blood pressure was unaffected treatment, but rate decreased 85%. ACEi-treated increased mesangial deposition type I collagen 105 kD complex collagenase activity. alpha 1 collagen, IV alpha-smooth muscle cell actin mRNAs. No changes were noted beta actin, 72 metalloproteinase The result net increase sclerosis. Surprisingly, treated with AngII developed marked arteriolar lesions. CONCLUSIONS: some forms glomerulosclerosis, lesions develop independently II. Pharmacological inhibition II, circumstance, may aggravate through disregulation levels degradation.