Skip to main content
Log in

The role of gender differences in beta-adrenergic receptor responsiveness of diabetic rat heart

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Since the mechanisms responsible for gender differences in cardiac contractile function have not been fully elucidated, we focused to determine the effect of gender difference on β-adrenergic receptors (β-ARs) signal transduction in ventricular cardiomyocytes from insulin-dependent diabetic (streptozotocin-induced) rats. Dose-response curves of left ventricular developed pressure (LVDP) to isoproterenol (ISO) in females showed that there was only a ∼30% decrease in the maximum response without a significant shift in EC50 in diabetic females. On the other hand, diabetes induced a clear rightward shift in the potency (5–10 folds) without a significant change in the maximum response in the males. In order to further determine of the underlying mechanism for this difference, we measured cAMP production and obtained dose-response curves with ISO stimulation in isolated cardiomyocytes. In diabetic females, there was no obvious change in the cAMP dose-response curve. On the other hand, there was a significant decrease in the maximum response without any apparent change in the potency of diabetic males. Our findings indicate that male and female rats are affected differently by diabetes in terms of LVDP responses to β-ARs stimulation. Also, the difference between their β-ARs induced cAMP responses may underlie this disparity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Schaible TF, Scheuer J (1984) Comparison of heart function in male and female rats. Basic Res Cardiol 79:404–412

    Article  Google Scholar 

  2. Schwertz DW, Beck JM, Kowalski JM, Ross JD (2004) Sex differences in the response of rat heart ventricle to calcium. Biol Res Nurs 5(4):286–298

    Article  PubMed  Google Scholar 

  3. Capasso JM, Remily RM, Smith RH, Sonnenblick EH (1983) Sex differences in myocardial contractility in the rat. Bas Res Cardiol 78:156–171

    Article  CAS  Google Scholar 

  4. Curl CL, Wendt IR, Kotsanas G (2001) Effects of gender on intracellular [Ca2+] in rat myocytes. Eur J Physiol 441:709–716

    Article  CAS  Google Scholar 

  5. Ayaz M, Ozdemir S, Ugur M, Vassort G, Turan B (2004) Effects of selenium on altered mechanical and electrical cardiac activities of diabetic rat. Arch Biochem Biophys 426:83–90

    Article  PubMed  CAS  Google Scholar 

  6. Ozdemir S, Ugur M, Gurdal H, Turan B (2005) Treatment with AT(1) receptor blocker restores diabetes-induced alterations in intracellular Ca(2+) transients and contractile function of rat myocardium. Arch Biochem Biophys 435:166–174

    Article  PubMed  CAS  Google Scholar 

  7. Bedinghaus J, Leshan L, Diehr S (2001) Coronary artery disease prevention: what’s different for women? Am Fam Physician 63:1393–1400

    PubMed  CAS  Google Scholar 

  8. Johnson BE, Johnson CA (2001) Cardiovascular disease and differences between the sexes. Am Fam Physician 63:1290–1292

    PubMed  CAS  Google Scholar 

  9. Stone PH, Thompson B, Anderson HV, Kronenberg MW, Gibson RS, Rogers WJ, Diver DJ, Theroux P, Warnica JW, Nasmith JB, Kells C, Kleiman N, McCabe CH, Schactman M, Knatterud GL, Braunwald E (1996) Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: the TIMI III registry. JAMA 275:1104–1112

    Article  PubMed  CAS  Google Scholar 

  10. Luzier AB, Nawarskas JJ, Anonuevo J, Wilson MF, Kazierad DJ (1998) The effects of gender on adrenergic receptor responsiveness. J Clin Pharmacol 38(7):618–624

    PubMed  CAS  Google Scholar 

  11. Rodrigues B, McNeill JH (1987) Comparison of cardiac function in male and female diabetic rats. Gen Pharmacol 18(4):421–423

    PubMed  CAS  Google Scholar 

  12. Sellers DJ, Chess-Williams R (2001) The effect of streptozotocin-induced diabetes on cardiac beta-adrenoceptor subtypes in the rat. J Autonomic Pharmacol 21(1):15–21

    Article  CAS  Google Scholar 

  13. Gando S, Hattori Y, Akaishi Y, Nishihira J, Kanno M (1997) Impaired contractile response to beta adrenoceptor stimulation in diabetic rat hearts: alterations in beta adrenoceptors-G protein-adenylate cyclase system and phospholamban phosphorylation. J Pharmacol Exp Ther 282:475–484

    PubMed  CAS  Google Scholar 

  14. Austin C, Williams RC (1993) The in-vitro effects of insulin and the effects of acute fasting on cardiac β-Adrenoceptor responses in the short-term streptozotocin-diabetic rat. J Pharm Pharmacol 46:326–331

    Google Scholar 

  15. Atkins FL, Dowell RT, Love S (1985) β-Adrenergic receptors, adenylate cyclase activity and cardiac dysfunction in the diabetic rat. J Cardiovasc Pharmacol 7:66–70

    Article  PubMed  CAS  Google Scholar 

  16. Kaul CL, Grewal RS (1980) Increased urinary excretion of catecholamines and their metabolites in streptozotocin diabetic rats. Pharmacology 21:223–228

    Article  PubMed  CAS  Google Scholar 

  17. Neubauer B, Christensen NJ (1976) Norepinephrine, epinephrine and dopamine contents of the cardiovascular system in long-term diabetes. Diabetes 25:6–10

    Article  PubMed  CAS  Google Scholar 

  18. Sato N, Hashimoto H, Takiguchi Y, Nakashima M (1989) Altered responsiveness to sympathetic nerve stimulation and agonists of isolated left atria of diabetic rats: no evidence for involvement of hypothyroidism. J Pharmacol Exp Ther 248:367–371

    PubMed  CAS  Google Scholar 

  19. Sayar K, Ugur M, Gurdal H, Onaran O, Hotomaroglu O, Turan B (2000) Dietary selenium and vitamin E intakes alter β-Adrenergic response of L-Type Ca-current and β-Adrenoceptor-Adenylate cyclase coupling in rat heart. J Nutr 130:733–740

    PubMed  CAS  Google Scholar 

  20. Brodde OE, Michel MC (1999) Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev 51(4):651–690

    PubMed  CAS  Google Scholar 

  21. Heyliger C, Pierce G, Singal P, Beamish R, Dhalla NS (1982) Cardiac alpha and beta-adrenergic receptor alterations in diabetic cardiomyopathy. Basic Res Cardiol 77:610–618

    Article  PubMed  CAS  Google Scholar 

  22. Ramanadham S, Tenner TE (1987) Alterations in the myocardial β-AR system of streptozotocin-diabetic rats. Eur J Pharmacol 136:377–389

    Article  PubMed  CAS  Google Scholar 

  23. Yu Z, McNeill JH (1991) Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy. J Pharmacol Exp Ther 257:257–264

    Google Scholar 

  24. Sunderesan PR, Sharma VK, Gingold SL, Banerjee PS (1984) Decreased beta adrenergic receptors in rat heart in streptozotocin-induced diabetes: role of thyroid hormones. Endocrinology 114:1358–1363

    Article  Google Scholar 

  25. Du XJ (2004) Gender modulates cardiac phenotype development in genetically modified mice. Cardiovasc Res 63:510–519

    Article  PubMed  CAS  Google Scholar 

  26. Dincer UD, Bidasee KR, Guner S, Tay A, Ozcelikay AT, Altan VM (2001) The effect of diabetes on expression of β1-, β2-, and β3-adrenoreceptors in rat hearts. Diabetes 50:455–461

    Article  PubMed  CAS  Google Scholar 

  27. Matsuda N, Hattori Y, Gando S, Akaishi Y, Kemnotsu O, Kanno M (1999) Diabetes-induced down-regulation of β1-AR mRNA expression in rat heart. Biochem Pharmacol 58:881–885

    Article  PubMed  CAS  Google Scholar 

  28. Minneman KP, Hedberg A, Molinoff PB (1979) Comparison of beta-adenergic receptor subtypes in mammalian tissues. J Pharmacol Exp Ther 211:502–508

    PubMed  CAS  Google Scholar 

  29. Bryan LJ, Cole JJ, O’Donnell SR, Wantstall JC (1981) A study designed to explore the hypothesis that beta-1 ARs are “innervated” receptors and beta-2 ARs are “hormonal” receptors. J Pharmacol Exp Ther 216:395–400

    PubMed  CAS  Google Scholar 

  30. Babiker FA, De Windt LJ, van Eickels M, Groke C, Meyer R, Doevendans PA (2002) Estrogenic hormone action in the heart: regulatory network and function. Cardiovasc Res 53:709–719

    Article  PubMed  CAS  Google Scholar 

  31. Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff E, Wenger N, HERS Research Group (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 288(1):49–57. Erratum in: JAMA 2002, 288(9):1064

    Google Scholar 

  32. Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wong ND, Crouse JR, Stein E, Cushman M, Women’s Health Initiative Investigators (2003) Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 49(6):523–534

    Google Scholar 

Download references

Acknowledgements

This work has been supported by grants of Ankara University project 2006-080-9233 and projects of TUBITAK-SBAG-PIA-10 (105S149) and TUBITAK-SBAG-3056 (104S591).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Belma Turan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bilginoglu, A., Amber Cicek, F., Ugur, M. et al. The role of gender differences in beta-adrenergic receptor responsiveness of diabetic rat heart. Mol Cell Biochem 305, 63–69 (2007). https://doi.org/10.1007/s11010-007-9528-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9528-0

Keywords

Navigation