Effect of Chronic Treatment with Losartan on Streptozotocin-induced Renal Dysfunction

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2003 Sep 6

PMID 12956402

Citations 2

Authors

B Murali

Dhananjay N Umrani

Ramesh K Goyal

Affiliations

Soon will be listed here.

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.

Citing Articles

Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease.

Jing M, Cen Y, Gao F, Wang T, Jiang J, Jian Q Front Pharmacol. 2021; 12:680336.

PMID: 34248629 PMC: 8264657. DOI: 10.3389/fphar.2021.680336.

Protective effect of herbomineral formulation (Dolabi) on early diabetic nephropathy in streptozotocin-induced diabetic rats.

Baig M, Gawali V, Patil R, Naik S J Nat Med. 2011; 66(3):500-9.

PMID: 22116744 DOI: 10.1007/s11418-011-0614-y.

References

Wald H, Scherzer P, Popovtzer M . Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. Circ Res. 1991; 68(4):1051-8. DOI: 10.1161/01.res.68.4.1051. View

Mogensen C, Christensen C . Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984; 311(2):89-93. DOI: 10.1056/NEJM198407123110204. View

Rasch R, Norgaard J . Renal enlargement: comparative autoradiographic studies of 3H-thymidine uptake in diabetic and uninephrectomized rats. Diabetologia. 1983; 25(3):280-7. DOI: 10.1007/BF00279944. View

Zatz R, Dunn B, Meyer T, Anderson S, Rennke H, Brenner B . Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. J Clin Invest. 1986; 77(6):1925-30. PMC: 370553. DOI: 10.1172/JCI112521. View

McCance R, WIDDOWSON E . Functional disorganization of the kidney in disease. J Physiol. 1939; 95(1):36-44. PMC: 1393957. DOI: 10.1113/jphysiol.1939.sp003709. View

Borch-Johnsen K, Andersen P, Deckert T . The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1985; 28(8):590-6. DOI: 10.1007/BF00281993. View

Burnier M, Waeber B, Brunner H . Clinical pharmacology of the angiotensin II receptor antagonist losartan potassium in healthy subjects. J Hypertens Suppl. 1995; 13(1):S23-8. DOI: 10.1097/00004872-199507001-00003. View

Mogensen C, Christensen C . Blood pressure changes and renal function in incipient and overt diabetic nephropathy. Hypertension. 1985; 7(6 Pt 2):II64-73. DOI: 10.1161/01.hyp.7.6_pt_2.ii64. View

Chatterjee P, Weerackody R, Mistry S, Hawksworth G, McLay J . Selective antagonism of the AT1 receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells. Kidney Int. 1997; 52(3):699-705. DOI: 10.1038/ki.1997.385. View

10.

Mazzocchi G, Malendowicz L, Gottardo G, Rebuffat P, Nussdorfer G . Angiotensin-II stimulates DNA synthesis in rat adrenal zona glomerulosa cells: receptor subtypes involved and possible signal transduction mechanism. Endocr Res. 1997; 23(3):191-203. DOI: 10.3109/07435809709031853. View

11.

Lafayette R, Mayer G, Park S, Meyer T . Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. J Clin Invest. 1992; 90(3):766-71. PMC: 329928. DOI: 10.1172/JCI115949. View

12.

. Renal hypertrophy in experimental diabetes mellitus. Kidney Int. 1983; 23(4):643-6. DOI: 10.1038/ki.1983.71. View

13.

Timmermans P, Wong P, Chiu A, Herblin W, Benfield P, Carini D . Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993; 45(2):205-51. View

14.

Rodrigues B, Goyal R, McNeill J . Effects of hydralazine on streptozotocin-induced diabetic rats: prevention of hyperlipidemia and improvement in cardiac function. J Pharmacol Exp Ther. 1986; 237(1):292-9. View

15.

Hricik D, Browning P, Kopelman R, Goorno W, Madias N, Dzau V . Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney. N Engl J Med. 1983; 308(7):373-6. DOI: 10.1056/NEJM198302173080706. View

16.

Brenner B, Schor N, Ichikawa I . Role of angiotensin II in the physiologic regulation of glomerular filtration. Am J Cardiol. 1982; 49(6):1430-3. DOI: 10.1016/0002-9149(82)90356-3. View

17.

Nielsen F, Rossing P, Gall M, Skott P, Smidt U, Parving H . Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes. 1994; 43(9):1108-13. DOI: 10.2337/diab.43.9.1108. View

18.

Cheng I, Ma J, Yeh G, Chan M . Comparison of captopril and enalapril in the treatment of hypertension in patients with non-insulin dependent diabetes mellitus and nephropathy. Int Urol Nephrol. 1990; 22(3):295-303. DOI: 10.1007/BF02550409. View

19.

Dunn B, Zatz R, Rennke H, Meyer T, Anderson S, Brenner B . Prevention of glomerular capillary hypertension in experimental diabetes mellitus obviates functional and structural glomerular injury. J Hypertens Suppl. 1986; 4(5):S251-4. View

20.

Vora J, Dolben J, Dean J, Thomas D, Williams J, Owens D . Renal hemodynamics in newly presenting non-insulin dependent diabetes mellitus. Kidney Int. 1992; 41(4):829-35. DOI: 10.1038/ki.1992.127. View