Share This Article:

Low Dose Irbesartan Has a Renoprotective Effect as High Dose Ramipril in Diabetic Rats Treated with Insulin

Abstract Full-Text HTML XML Download Download as PDF (Size:1911KB) PP. 149-161
DOI: 10.4236/ojemd.2015.511019    2,878 Downloads   3,251 Views  

ABSTRACT

Objectives: The aim of this study is to compare the efficacy of the anti-angiotensinic drug, ramipril and irbesartan on the vascular protection of kidneys of streptozotocin (STZ)-induced diabetic rats (DR). Methods: 110 male albino rats were divided into 7 main groups. Group-1 (10 normal control rats; NC). Group-2 (10 rats) was injected intra-peritoneally with STZ (Diabetic Rats; DR). Group-3 (10 DR) is controlled by insulin. Groups 4 to 7 (20 DR), each is subdivided into two subgroups that received either low or high dose of ramipril or irbesartan with or without insulin. Two months post treatment, rat-tail blood was collected to measure: Fasting blood sugar, HbA1c, total serum proteins, albumin and lipid profiles. Urine was collected to measure albuminuria. Kidneys were isolated for histopathological study. Results: Biochemically, both ramipril and irbesartan (without insulin) lowered albumin concentration in urine samples especially at high doses. Histopathologically, there is no beneficial response of both drugs without insulin. Combination of insulin together with either drug has beneficial effects biochemically and histopathologically at high doses. Low dose irbesartan only has renoprotective effect in DR treated with insulin. The other biochemical parameters showed negligible response to both drugs. Conclusion: Low dose irbesartan and high doses of both drugs have renoprotective effect in DR treated with insulin.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Alqasim, A. , Hammadi, S. , Bamagous, G. , Noureldin, E. and Madi, H. (2015) Low Dose Irbesartan Has a Renoprotective Effect as High Dose Ramipril in Diabetic Rats Treated with Insulin. Open Journal of Endocrine and Metabolic Diseases, 5, 149-161. doi: 10.4236/ojemd.2015.511019.

References

[1] Eurich, D.T., Weir, D.L., Majumdar, S.R., Tsuyuki, R.T., Johnson, J.A., Tjosvold, L., et al. (2013) Comparative Safety and Effectiveness of Metformin in Patients with Diabetes Mellitus and Heart Failure: Systematic Review of Observational Studies Involving 34,000 Patients. Circulation Heart Failure, 6, 395-402. http://dx.doi.org/10.1161/CIRCHEARTFAILURE.112.000162
[2] Kliger, A.S., Foley, R.N., Goldfarb, D.S., Goldstein, S.L., Johansen, K., Singh, A., et al. (2013) KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. American Journal of Kidney Diseases, 62, 849-859. http://dx.doi.org/10.1053/j.ajkd.2013.06.008
[3] Ravid, M., Lang, R., Rachmani, R. and Lishner, M. (1996) Long-Term Renoprotective Effect of Angiotensin-Converting Enzyme Inhibition in Non-Insulin-Dependent Diabetes Mellitus. A 7-Year Follow-Up Study. Archives of Internal Medicine, 156, 286-289.
http://dx.doi.org/10.1001/archinte.1996.00440030080010
[4] UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes (UKPDS 33). Lancet, 352, 837-853.
http://dx.doi.org/10.1016/S0140-6736(98)07019-6
[5] Ismail-Beigi, F., Craven, T., Banerji, M.A., Basile, J., Calles, J., Cohen, R.M., et al. (2010) Effect of Intensive Treatment of Hyperglycaemia on Microvascular Outcomes in Type 2 Diabetes: An Analysis of the ACCORD Randomised trial. Lancet, 376, 419-430. http://dx.doi.org/10.1016/S0140-6736(10)60576-4
[6] Lewington, S., Clarke, R., Qizilbash, N., Peto, R. and Collins, R., Prospective Studies C. (2002) Age-Specific Relevance of Usual Blood Pressure to Vascular Mortality: A Meta-Analysis of Individual Data for One Million Adults in 61 Prospective Studies. Lancet, 360, 1903-1913.
http://dx.doi.org/10.1016/S0140-6736(02)11911-8
[7] The Diabetes Control and Complications (DCCT) Research Group (1995) Effect of Intensive Therapy on the Development and Progression of Diabetic Nephropathy in the Diabetes Control and Complications Trial. Kidney International, 47, 1703-1720. http://dx.doi.org/10.1038/ki.1995.236
[8] Sen, S., Kanter, M., Ustundag, S., Aktas, C., Dogutan, H. and Yalcin, O. (2008) Effect of Angiotensin-Converting enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade on Streptozotocin-Induced Diabetic Nephropathy. Renal Failure, 30, 1023-1033. http://dx.doi.org/10.1080/08860220802495248
[9] Laffel, L.M., McGill, J.B. and Gans, D.J. (1995) The Beneficial Effect of Angiotensin-Converting Enzyme Inhibition with Captopril on Diabetic Nephropathy in Normotensive IDDM Patients with Microalbuminuria. North American Microalbuminuria Study Group. The American Journal of Medicine, 99, 497-504. http://dx.doi.org/10.1016/S0002-9343(99)80226-5
[10] Remuzzi, G., Macia, M. and Ruggenenti, P. (2006) Prevention and Treatment of Diabetic Renal Disease in Type 2 Diabetes: The BENEDICT Study. Journal of the American Society of Nephrology, 17, S90-S97. http://dx.doi.org/10.1681/ASN.2005121324
[11] Psaty, B.M., Lumley, T., Furberg, C.D., Schellenbaum, G., Pahor, M., Alderman, M.H., et al. (2003) Health Outcomes Associated with Various Antihypertensive Therapies Used as First-Line Agents: A Network Meta-Analysis. JAMA, 289, 2534-2544. http://dx.doi.org/10.1001/jama.289.19.2534
[12] Haller, H., Ito, S., Izzo Jr., J.L., Januszewicz, A., Katayama, S., Menne, J., et al. (2011) Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes. The New England Journal of Medicine, 364, 907-917. http://dx.doi.org/10.1056/NEJMoa1007994
[13] Bilous, R., Chaturvedi, N., Sjolie, A.K., Fuller, J., Klein, R., Orchard, T., et al. (2009) Effect of Candesartan on Microalbuminuria and Albumin Excretion Rate in Diabetes: Three Randomized Trials. Annals of Internal Medicine, 151, 11-20.
[14] Mauer, M., Zinman, B., Gardiner, R., Suissa, S., Sinaiko, A., Strand, T., et al. (2009) Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes. The New England Journal of Medicine, 361, 40-51. http://dx.doi.org/10.1056/NEJMoa0808400
[15] Parving, H.H., Lehnert, H., Brochner-Mortensen, J., Gomis, R., Andersen, S., Arner, P., et al. (2001) The Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes. The New England Journal of Medicine, 345, 870-878. http://dx.doi.org/10.1056/NEJMoa011489
[16] Schjoedt, K.J., Jacobsen, P., Rossing, K., Boomsma, F. and Parving, H.H. (2005) Dual Blockade of the Renin-Angiotensin-Aldosterone System in Diabetic Nephropathy: The Role of Aldosterone. Hormone and Metabolic Research, 37, 4-8.
[17] Schjoedt, K.J., Rossing, K., Juhl, T.R., Boomsma, F., Rossing, P., Tarnow, L., et al. (2005) Beneficial Impact of Spironolactone in Diabetic Nephropathy. Kidney International, 68, 2829-2836.
http://dx.doi.org/10.1111/j.1523-1755.2005.00756.x
[18] Masiello, P., Broca, C., Gross, R., Roye, M., Manteghetti, M., Hillaire-Buys, D., et al. (1998) Experimental NIDDM: Development of a New Model in Adult Rats Administered Streptozotocin and Nicotinamide. Diabetes, 47, 224-229. http://dx.doi.org/10.2337/diab.47.2.224
[19] Matsumoto, H., Uchino, M. and Kato, M. (2013) Evaluation of Haemoglobin A1c Measurement by an Enzymatic Method Using an Automated Analyser That Has an On-Board Haemolysis System. Annals of Clinical Biochemistry, 50, 443-449. http://dx.doi.org/10.1177/0004563213476859
[20] Niskanen, L., Turpeinen, A., Penttila, I. and Uusitupa, M.I. (1998) Hyperglycemia and Compositional Lipoprotein Abnormalities as Predictors of Cardiovascular Mortality in Type 2 Diabetes: A 15-Year Follow-Up from the Time of Diagnosis. Diabetes Care, 21, 1861-1869.
http://dx.doi.org/10.2337/diacare.21.11.1861
[21] Agrawal, B., Berger, A., Wolf, K. and Luft, F.C. (1996) Microalbuminuria Screening by Reagent Strip Predicts Cardiovascular Risk in Hypertension. Journal of Hypertension, 14, 223-228.
http://dx.doi.org/10.1097/00004872-199602000-00011
[22] Shulman, N.B., Ford, C.E., Hall, W.D., Blaufox, M.D., Simon, D., Langford, H.G., et al. (1989) Prognostic Value of Serum Creatinine and Effect of Treatment of Hypertension on Renal Function. Results from the Hypertension Detection and Follow-Up Program. The Hypertension Detection and Follow-Up Program Cooperative Group. Hypertension, 13, I80-I93. http://dx.doi.org/10.1161/01.HYP.13.5_Suppl.I80
[23] Hoogeveen, E.K., Kostense, P.J., Jager, A., Heine, R.J., Jakobs, C., Bouter, L.M., et al. (1998) Serum Homocysteine Level and Protein Intake Are Related to Risk of Microalbuminuria: The Hoorn Study. Kidney International, 54, 203-209. http://dx.doi.org/10.1038/sj.ki.4495353
[24] Forsblom, C.M., Groop, P.H., Ekstrand, A., Totterman, K.J., Sane, T., Saloranta, C., et al. (1998) Predictors of Progression from Normoalbuminuria to Microalbuminuria in NIDDM. Diabetes Care, 21, 1932-1938. http://dx.doi.org/10.2337/diacare.21.11.1932
[25] Stehouwer, C.D., Nauta, J.J., Zeldenrust, G.C., Hackeng, W.H., Donker, A.J. and den Ottolander, G.J. (1992) Urinary Albumin Excretion, Cardiovascular Disease, and Endothelial Dysfunction in Non-Insulin-Dependent Diabetes Mellitus. The Lancet, 340, 319-323.
http://dx.doi.org/10.1016/0140-6736(92)91401-S
[26] Chobanian, A.V., Hope, S. and Brecher, P. (1995) Dissociation between the Antiatherosclerotic Effect of Trandolapril and Suppression of Serum and Aortic Angiotensin-Converting Enzyme Activity in the Watanabe Heritable Hyperlipidemic Rabbit. Hypertension, 25, 1306-1310.
http://dx.doi.org/10.1161/01.HYP.25.6.1306
[27] Lonn, E., Yusuf, S., Dzavik, V., Doris, C., Yi, Q., Smith, S., et al. (2001) Effects of Ramipril and Vitamin E on Atherosclerosis: The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE). Circulation, 103, 919-925. http://dx.doi.org/10.1161/01.CIR.103.7.919
[28] Rabbat, C.G. (2002) Irbesartan Was Renoprotective in Patients with Type 2 Diabetes, Hypertension, and Microalbuminuria. ACP Journal Club, 136, 82-84.
[29] Maillard, M.P., Wurzner, G., Nussberger, J., Centeno, C., Burnier, M. and Brunner, H.R. (2002) Comparative Angiotensin II Receptor Blockade in Healthy Volunteers: The Importance of Dosing. Clinical Pharmacology and Therapeutics, 71, 68-76. http://dx.doi.org/10.1067/mcp.2002.121425
[30] Kagami, S., Border, W.A., Miller, D.E. and Noble, N.A. (1994) Angiotensin II Stimulates Extracellular Matrix Protein Synthesis through Induction of Transforming Growth Factor-Beta Expression in Rat Glomerular Mesangial Cells. The Journal of Clinical Investigation, 93, 2431-2437.
http://dx.doi.org/10.1067/mcp.2002.121425
[31] Osei, S.Y., Price, D.A., Laffel, L.M., Lansang, M.C. and Hollenberg, N.K. (2000) Effect of Angiotensin II Antagonist Eprosartan on Hyperglycemia-Induced Activation of Intrarenal Renin-Angiotensin System in Healthy Humans. Hypertension, 36, 122-126. http://dx.doi.org/10.1161/01.HYP.36.1.122
[32] Zatz, R., Dunn, B.R., Meyer, T.W., Anderson, S., Rennke, H.G. and Brenner, B.M. (1986) Prevention of Diabetic Glomerulopathy by Pharmacological Amelioration of Glomerular Capillary Hypertension. The Journal of Clinical Investigation, 77, 1925-1930. http://dx.doi.org/10.1172/JCI112521
[33] Abbate, M., Zoja, C., Corna, D., Capitanio, M., Bertani, T. and Remuzzi, G. (1998) In Progressive Nephropathies, Overload of Tubular Cells with Filtered Proteins Translates Glomerular Permeability Dysfunction into Cellular Signals of Interstitial Inflammation. Journal of the American Society of Nephrology: JASN, 9, 1213-1224.
[34] Wolf, G., Haberstroh, U. and Neilson, E.G. (1992) Angiotensin II Stimulates the Proliferation and Biosynthesis of Type I Collagen in Cultured Murine Mesangial Cells. The American Journal of Pathology, 140, 95-107.
[35] Ruggenenti, P., Perna, A., Gherardi, G., Benini, R. and Remuzzi, G. (2000) Chronic Proteinuric Nephropathies: Outcomes and Response to Treatment in a Prospective Cohort of 352 Patients with Different Patterns of Renal Injury. American Journal of Kidney Diseases: The Official Journal of the National Kidney Foundation, 35, 1155-1165. http://dx.doi.org/10.1016/S0272-6386(00)70054-0
[36] Ravid, M., Savin, H., Jutrin, I., Bental, T., Katz, B. and Lishner, M. (1993) Long-Term Stabilizing Effect of Angiotensin-Converting Enzyme Inhibition on Plasma Creatinine and on Proteinuria in Normotensive Type II Diabetic Patients. Annals of Internal Medicine, 118, 577-581.
http://dx.doi.org/10.7326/0003-4819-118-8-199304150-00001
[37] Lewis, E.J., Hunsicker, L.G., Clarke, W.R., Berl, T., Pohl, M.A., Lewis, J.B., et al. (2001) Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes. The New England Journal of Medicine, 345, 851-860. http://dx.doi.org/10.1056/NEJMoa011303
[38] Heart Outcomes Prevention Evaluation (HOPE) Study Investigators (2000) Effects of Ramipril on Cardiovascular and Microvascular Outcomes in People with Diabetes Mellitus: Results of the HOPE Study and MICRO-HOPE Substudy. The Lancet, 355, 253-259.
http://dx.doi.org/10.1016/S0140-6736(99)12323-7
[39] Mogensen, C.E., Keane, W.F., Bennett, P.H., Jerums, G., Parving, H.H., Passa, P., et al. (1995) Prevention of Diabetic Renal Disease with Special Reference to Microalbuminuria. The Lancet, 346, 1080-1084. http://dx.doi.org/10.1016/S0140-6736(95)91747-0
[40] American Diabetes Association (2014) Standards of Medical Care in Diabetes—2014. Diabetes Care, 37, S14-S80. http://dx.doi.org/10.2337/dc14-S014

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.