Abstract
The present investigation was undertaken to study the effect of chronic treatment with angiotensin (AT1) receptor antagonist losartan (2 mg/kg, p.o., 6 weeks) on streptozotocin (STZ) induced (45 mg/kg, i.v., single dose) renal dysfunctions in diabetic rats. Injection of streptozotocin produced not only the cardinal symptoms of diabetes mellitus like loss of body weight, hyperglycemia, and hypoinsulinemia but also the renal dysfunctions. Losartan treatment significantly prevented all these changes except STZ-induced hypoinsulinemia. There was a significant elevation of blood pressure in diabetic rats and treatment with losartan significantly brought it back to normal. Renal dysfunction in diabetic rats was characterized by a significant decrease in creatinine clearance, elevated levels of electrolytes and renal hypertrophy. Treatment with losartan prevented these changes. A good correlation was found between biochemical parameters and histopathological abnormalities. Our data suggests that, losartan may be considered as the drug of choice when there is a co-existence of diabetes mellitus and hypertension with compromised kidney function.
Similar content being viewed by others
References
Borch-Johnsen K, Andersen PK, Deckert T: The effect of proteinuria on relative mortality in type I (insulin-dependent diabetes mellitus. Diabetologia 28: 590-596, 1985
Vora JP, David J, David W, Peterson RO: Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus. Kidney Int 41: 829-835, 1992
Rettig B, Teusch SM: The incidence of end stage renal failure in type I and type II diabetes mellitus. Diabetic Nephrol 3: 26-27, 1992
Flemming SN, Peter R, Mari AG, Peter S, Ulla MS, Parving HH: Impact of Lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes 43: 1108-1113, 1994
Michel M: Diabetic nephropathy: The ACE hypothesis. J Dia Comp 10: 126-128, 1996
Friberg P, Sundelin B, Bohman SO, Bobik A, Nilsson H, Wickman A, Gustafsson H, Peterson J, Adams MA: Renin-angiotensin system in neonatal rats: Induction of renal abnormality in response to ACE inhibition or angiotensin II antagonism. Kidney Int 45: 485-492, 1994
Zatz R, Dunn BR, Meyer TW, Anderson S, Rennke HG, Brenner BM: Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest 77: 1925-1930, 1986
Goyal RK, Lakkad NB, Rao MV: Effects of chronic treatment with enalapril on streptozotocin induced diabetic rats. Pharmacol Rev Comm 5: 201-209, 1997
Cheng IKP, Ma JTC, Yeh GR, Chan MK: Comparison of captopril and enalapril in the treatment of hypertension in patients with non-insulin dependent diabetes mellitus and nephropathy. Int Urol Nephrol 22: 295-303, 1990
Hommel E, Parving HH, Mathiesen E, Edsberg B, Nielson MD, Giese J: Effect of capropril on kidney function in insulin dependent diabetic patients with nephropathy. Br Med J 293: 467-470, 1986
Mogensen CE, Christensen CK: Predicting diabetic nephropathy in insulin dependent patients. N Eng J Med 311: 89-93, 1984
Anderson S, Rannke HG, Garcia DL, Brenner BM: Short and long term effects of antihypertensive therapy in diabetic rat. Kidney Int 36: 526-536, 1989
Lowry OH, Rosebrough NJ, Farr AI, Randall RJ: Protein measurement with folin phenol reagent. J Biol Chem 193: 265-275, 1951
Sevak AR, Goyal RK: Effects of chronic treatment with lisinopril on cardiovascular complications in streptozotocin-induced diabetic and DOCA hypertensive rats. Pharm Res 34: 201-209, 1996
Kawashima H: Chronic hypertension induced by STZ in rats. Naunyn Schiemedberg Arch Pharmacol 305: 123-126, 1978
Rodrigues B, Goyal RK, McNeill JH: Effects of hydralazine on STZ-induced diabetic rats — prevention of hyperlipidaemia and improvement in cardiac function. J Pharmacol Exp Ther 237: 292-299, 1986
Ritz E, Hasslacher C, Guo J-Z, Mann JFE: Role of hypertension in diabetic nephropathy. In: A. Heidland, K.M. Koch, E. Heidbrder (ed). Diabetes and the Kidney. Basal Krager, 1989, pp 91-101
Mogensen CE, Christensen CK: Blood pressure changes and renal function in incipient and over diabetic nephropathy. Hypertension 7: 1164-1173, 1985
McCance RA, Widdowson EM: Functional disorganization of the kidney in disease. J Physiol 95: 36-44, 1939
Dunn B R, Zatz R: Prevention of glomerular capillary hypertension in experimental diabetes mellitus obviates functional and structural glomerular injury. J Hypertens 4: S251-S254, 1986
Valvo E, Bedogna V, Casagrande P: Captopril in patients with type II diabetes and renal insufficiency: Systemic and renal hemodynamic alterations. Am J Med 85: 344-348, 1988
Bjorck S, Mulec H, Johnsen SA: Contrasting effects of enalapril and metoprolol on proteinuria in diabetic nephropathy. Br Med J 300: 904-907, 1990
Hricik DE, Browning PJ, Kopelman R, Goorno WE, Madias NE, Dzau VJ: Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenosis or renal-artery stenosis in a solitary kidney. N Eng J Med 308: 373-375, 1983
Taguma Y, Katamote Y, Futaki G, Veda H, Nonma H, Bhizaki M, Takakashi H, Seiko H, Sasaki Y: Effects of captopril on heavy proteinuria in azotemic diabetes. N Eng J Med 313: 1617-1620, 1985
Zimmerman BG: Adrenergic facilitation by angiotesin: Does it serve a physiological function? Clin Sci 60: 343-348, 1981
Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JM, Smith RD: Angiotensin II receptors and angiotensin II receptor antagonists. Pharm Rev 45: 205-251, 1993
Hansen SK: Renal hypertrophy in experimental diabetes. Kidney Int 23: 643-646, 1983
Cortes P, Dumler F, Venkatachalam KK, Levin NW: Effects of diabetes mellitus on renal metabolism. Minor Electrolyte Metab 9: 306-316, 1983
Rash R, Rytter-Norgaard JO: Renal enlargement: Comparative autoradiographic studies of 3H-thymidine uptake in diabetic and uninephrectomized rats. Diabetalogia 25: 280-287, 1983
Mazzocchi G, Malendowicz LK, Gottardo G, Rebuffat P, Nussdorfer GG.: Angiotensin II stimulates DNA synthesis in rat adrenal zona glomerulosa cells: Receptor subtypes involved and possible signal transduction mechanism. End Res 23: 191-203, 1983
Chatterjee PK, Weerackody RP, Mistry SK, Hawksworth GM, McLay JS: Selective antagonism of the AT1 receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells. Kidney Int 52: 699-705, 1997
Burnier M, Waeber B, Brunner HR: Clinical pharmacology of the angiotensin II receptor antagonist losartan potassium in healthy subjects. J Hypertens 31(suppl): S23-S28, 1995
Wald H, Scherzer P, Popovtzer MM: Na, K-ATPase in isolated nephron segments in rats with experimental heart failure. Circ Res 68: 1051-1058, 1991
Brenner BM, Schor N, Ichikawa I: Role of angiotensin-II in the physiologic regulation of glomerular filtration. Am J Cardiol 49: 1430-1433, 1982
Lafayette RA, Mayer G, Park SK, Mayer TW: Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. J Clin Invest 90: 766-771, 1992
William FK, Sharon A, Mattias A, Dick DZ, Robertm GN, Gail P: Angiotensin converting enzyme inhibitors and progressive renal insufficiency. Ann Int Med 111: 503-516, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Murali, B., Umrani, D.N. & Goyal, R.K. Effect of chronic treatment with losartan on streptozotocin-induced renal dysfunction. Mol Cell Biochem 249, 85–90 (2003). https://doi.org/10.1023/A:1024707326943
Issue Date:
DOI: https://doi.org/10.1023/A:1024707326943