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The effects of telmisartan on mechanical responses of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus

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Abstract

The purpose of this study was to investigate the effects of telmisartan (5 × 10−5 M) on the mechanical response of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus. We studied 32 rats; 16 were rendered diabetic by a single intravenous injection of streptozotocin (45 mg kg−1 i.v.) and 16 formed a non-diabetic control group. Diabetic animals were divided into two groups: diabetic-telmisartan group and the diabetic-control group. Non-diabetic controls were further divided into the non-diabetic-telmisartan group and the non-diabetic-control group. We found: (1) Muscle twitch tension (P 0) and contraction and relaxation rates were significantly lower in diabetic controls than in the other groups. (2) Telmisartan significantly increased P 0 in both diabetic and non-diabetic rats. (3) Times to peak tension and half-relaxation were significantly greater in groups DC and DT than in the non-diabetics. In conclusion, our data suggest that telmisartan attenuates diabetes-induced impairment of diabetic rat papillary muscles, and may thus be able to reduce cardiac complications in diabetes.

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References

  1. Tschoepe D, Menart-Houtermans B (2002) Diabetes mellitus. In: Michelson AD (ed) Platelets. Academic Press, San Diego, pp 435–445

    Google Scholar 

  2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234

    Article  CAS  PubMed  Google Scholar 

  3. Kavak S, Emre M, Tetıker T, Kavak T, Kolcu Z, Günay İ (2008) Effects of rosiglitazone on altered electrical left ventricular papillary muscle activities of diabetic rat. Naunyn–Schmiedeberg’s Arch Pharmacol 376(6):415–421

    Article  CAS  Google Scholar 

  4. Aomine M, Yamato T (2000) Electrophysiological properties of ventricular muscle obtained from spontaneously diabetic mice. Exp Anim 49(1):23–33

    Article  CAS  PubMed  Google Scholar 

  5. Makino N, Dhalla KS, Elimban V, Dhalla NS (1987) Sarcolemmal Ca2+ transport in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol 253(2 Pt 1):E202–E207

    CAS  PubMed  Google Scholar 

  6. Nobe S, Aomine M, Arita M, Ito S, Takaki R (1990) Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: circumstantial evidence for impaired Ca2+ channel. Cardiovasc Res 24(5):381–389

    Article  CAS  PubMed  Google Scholar 

  7. Wang DW, Kiyosue T, Shigematsu S, Arita M (1995) Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rat with chronic diabetes. Am J Physiol 269:HI288–HI296

    Google Scholar 

  8. Yu Z, Tibbits GF, McNeill JH (1994) Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding. Am J Physiol 266(5 Pt 2):H2082–H2089

    CAS  PubMed  Google Scholar 

  9. Fang ZY, Prins JB, Marwick TH (2004) Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev 25:543–567

    Article  CAS  PubMed  Google Scholar 

  10. Galderisi M, Anderson KM, Wilson PW, Levy D (1991) Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol 68(1):85–89

    Article  CAS  PubMed  Google Scholar 

  11. Privratsky JR, Wold LE, Sowers JR, Quinn MT, Ren J (2003) AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT 1 receptor and NADPH oxidase. Hypertension 42:206–212

    Article  CAS  PubMed  Google Scholar 

  12. Wienen W, Hauel N, van Meel JC, Narr B, Ries U, Entzeroth M (1993) Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist, BIBR 277. Br J Pharmacol 110:245–252

    CAS  PubMed  Google Scholar 

  13. Pershadsingh HA, Kurtz TW (2004) Insulin-sensitizing effects of telmisartan: implications for treating insulin-resistant hypertension and cardiovascular disease. Diabetes Care 27:1015

    Article  PubMed  Google Scholar 

  14. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, Qi N, Wang J, Avery MA, Kurtz TW (2004) Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-c-modulating activity. Hypertension 43:993–1002

    Article  CAS  PubMed  Google Scholar 

  15. Böhm M, Lee M, Kreutz R et al (1995) Angiotensin II receptor blockade in TGR(mREN2)27: effects of renin-angiotensin system gene expression and cardiovascular functions. Hypertension 13:891–899

    Article  Google Scholar 

  16. Böhm M, Lippoldt A, Wienen W, Ganten D, Bader M (1996) Reduction of cardiac hypertrophy in TGR(mREN2) 27 by angiotensin II receptor blockade. Mol Cell Biochem 163/164:217–221

    Article  Google Scholar 

  17. Wagner J, Drab M, Bohlender J, Amann K, Wienen W, Ganten D (1998) Effects of AT1 receptor blockade on blood pressure and the renin-angiotensin system in spontaneously hypertensive rats of the stroke prone strain. Clin Exp Hypertens 20:205–221

    Article  CAS  PubMed  Google Scholar 

  18. Bonnevie-Nielsen V, Steffes MW, Lernmark A (1981) A major loss in islet mass and B-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin. Diabetes 30:424–429

    Article  CAS  PubMed  Google Scholar 

  19. Ramesh B, Pugalendi KV (2007) Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharmacol Rep 59:349–358

    Google Scholar 

  20. Bracken N, Howarth FC, Sıngh J (2006) Effects of streptozotocin-induced diabetes on contraction and calcium transport in rat ventricular cardiomyocytes. Ann NY Acad Sci 1084:208–222

    Article  CAS  PubMed  Google Scholar 

  21. Brown RA, Lee MM, Sundareson AM, Woodbury DJ, Savage AO (1996) Influence of calcium channel blocker treatment on the mechanical properties of diabetic rat myocardium. Acta Diabetol 33:7–14

    Article  CAS  PubMed  Google Scholar 

  22. Ren J, Walsh MF, Sowers JR, Brown RA (1999) Augmentation of the inotropic response to insulin in diabetic rat hearts. Life Sci 65:369–380

    Article  CAS  PubMed  Google Scholar 

  23. Morimoto S, Yano Y, Maki K, Sawada K (2006) Renal and vascular protective effects of telmisartan in patients with essential hypertension. Hypertens Res 29:567–572

    Article  CAS  PubMed  Google Scholar 

  24. Remuzzi A, Remuzzi G (2006) Potential protective effects of telmisartan on renal function deterioration. JRAAS 7:185–191

    CAS  PubMed  Google Scholar 

  25. Schafer A, Flierl U, Vogt C, Menninger S, Tas P, Ertl G, Bauersachs J (2007) Telmisartan improves vascular function and reduces platelet activation in rats with streptozotocin-induced diabetes mellitus. Pharmacol Res 56:217–223

    Article  PubMed  Google Scholar 

  26. Wienen W, Richard S, Champeroux P, Audeval-Gerard C (2001) Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats. JRAAS 2:31–36

    CAS  PubMed  Google Scholar 

  27. Cheetham C, O’Driscoll G, Stanton K et al (2001) Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in type II diabetes. Clin Sci (Lond) 100:13–17

    Article  CAS  Google Scholar 

  28. Ohmura T, Tsunenari I, Seidler R, Chachin M, Hayashi T, Konomi A, Matsumaru T, Sumida T, Hayashi N, Horie Y (2007) Renoprotective effects of telmisartan on renal injury in obese Zucker rats. Acta Diabetol. Nov 16

  29. Horie Y (2007) Renoprotective effects of telmisartan in the 5/6 nephrectomised rats. J Renin Angiotensin Aldosterone Syst 8(2):93–100

    Article  PubMed  Google Scholar 

  30. Brenner BM, Cooper ME, de Zeeuw D et al (2001) Effects of losartan on renal and cardio-vascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    Article  CAS  PubMed  Google Scholar 

  31. Sechi LA, Griffin CA, Schambelan M (1994) The cardiac renin-angiotensin system in STZ-induced diabetes. Diabetes 43:e1180–e1184

    Article  Google Scholar 

  32. Ren J, Davidoff AJ (1997) Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes. Am J Physiol Heart Circ Physiol 272:H148–H158

    CAS  Google Scholar 

  33. Dutta K, Podolin DA, Davidson MB, Davidoff AJ (2001) Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance. Diabetes 50:1186–1192

    Article  CAS  PubMed  Google Scholar 

  34. Wold LE, Relling DP, Colligan PB, Scott GI, Hintz KK, Ren BH, Epstein PN, Ren J (2001) Characterization of contractile function in diabetic hypertensive cardiomyopathy in adult rat ventricular myocytes. J Mol Cell Cardiol 33:1719–1726

    Article  CAS  PubMed  Google Scholar 

  35. Zolk O, Flesch M, Nickenig G, Schnabel P, Böhm M (1998) Alteration of intracellular Ca2+-handling and receptor regulation in hypertensive cardiac hypertrophy: insights from Ren2-transgenic rats. Cardiovasc Res 39(1):242–256

    Article  CAS  PubMed  Google Scholar 

  36. Ozdemir S, Ugur M, Gürdal H, Turan B (2005) Treatment with AT1 receptor blocker restores diabetes-induced alterations in intracellular Ca2+ transients and contractile function of rat myocardium. Arch Biochem Biophys 435:166–174

    Article  CAS  PubMed  Google Scholar 

  37. Ishikawa T, Kajiwara H, Kurihara S (1999) Am J Physiol 277: H2185–H2194

    Google Scholar 

  38. Satoh N, Sato T, Shimada M, Yamada K, Kitada Y (2001) J Pharm Exp Ther 298: 1161–1166

    Google Scholar 

  39. Trost SU, Belke DD, Bluhm WF, Meyer M, Swanson E, Dillmann WH (2002) Diabetes 51: 1166–1171

    Google Scholar 

  40. Lagadic-Gossmann D, Buckler KJ, Le Prigent K, Feuvray D (1996) Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 270:H1529–H1537

    CAS  PubMed  Google Scholar 

  41. Makino N, Dhalla KS, Elimban V, Dhalla NS (1987) Sarcolemmal transport in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol 253 (Endocrinol Metab 16): E202–E207

  42. Penpargkul S, Fein F, Sonnenblick EH, Scheuer J (1981) Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol 13:303–309

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Çukurova University Research Projects Department (No. TF2006BAP32).

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Authors and Affiliations

  1. Department of Biophysics, School of Medicine, Cukurova University, 01330, Adana, Turkey

    Mustafa Emre & Servet Kavak

  2. Department of Anesthesiology, School of Medicine, Cukurova University, Adana, Turkey

    Hakki Unlugenc

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  1. Mustafa Emre
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  2. Servet Kavak
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Correspondence to Mustafa Emre.

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Emre, M., Kavak, S. & Unlugenc, H. The effects of telmisartan on mechanical responses of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus. Acta Diabetol 47 (Suppl 1), 153–159 (2010). https://doi.org/10.1007/s00592-009-0156-x

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  • DOI: https://doi.org/10.1007/s00592-009-0156-x

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