STUDY OF RELATION SHIP BETWEEN TOXICITY OF GENTAMICIN AND ACTIVITY OF SERUM AND TISSUE ANGIOTENSIN CONVERTING ENZYME IN RAT

Angiotensin I-converting enzyme (ACE) converts the inactive angiotensin I molecule to the active angiotensin II. ACE is abundant in epithelium, endothelium and neuroepithelial cells so it found largely on the brush border of intestine and kidney proximal tubules. ACE also presents in the serum. Some pulmonary and renal toxic drugs change the serum and tissue ACE contents. In this study changesin ACE activity was studied in gentamicin induced renal failure of rats. Rats were sacrificed 1, 3, 5 and 7 days after intrapritoneal injection of 100 mg/kg of Gentamicin and ACE activity was measured in serum, kidney and lung. These data were compared with vehicle-treated rats. Rats with acute renal failure had proteinuria, polyuria, and decreased creatinin clearance. The damage to the proximal tubule of kindy was evident by (a) the histological analysis at light microscopy and (b) the augmentation in the urinary excretion of NAG. (N-acetyl β-D-glucosaminidase) Kidney ACE activity significantly decreased and lung and serum ACE activity didn’t change until 7 th day. Then lung ACE activity increased significantly at 7 th day as well as kidney and serum ACE activity. Blood pressure increased significantly on the 7 th day correspond with the increment in lung ACE activity. These data support the idea that kidney ACE activity decrease are due to local nitric oxide release in damaged kidney, and this effect reversed by an universal signal which increase ACE contents in the body probably to increase systemic blood pressure and subsequently increase glomerular filtration rate (GFR).