Abstract
A number of investigations in humans and animals suggest that there may be intrinsic sex-associated differences in cardiac function. Using left atrial preparations from male and female rat hearts, we examined differences in myocardial function and response to adrenergic agonists. Contractile parameters were measured in isolated atria by conventional isometric methods in the absence or presence of isoproterenol or phenylephrine. Responsiveness to Ca2+ was measured in detergent-skinned atrial fibers and actomyosin ATPase activity was measured in isolated myofibrils. Tetanic contractions were generated by treating the atrium with ryanodine followed by high frequency stimulation. Developed force was greater and maximal rates of contraction and relaxation were more rapid in the female atrium. The relationship between Ca2+ concentration and force in both intact atria and detergent-skinned atrial fibers in females fell to the left of that for males. At low Ca2+ concentrations, skinned fibers from female atria generated more force and myofibrils from female atria had higher myosin ATPase activity than males. Tetanic contraction in the presence of high extracellular Ca2+ was greater in female atria. Male atrium had larger inotropic responses to isoproterenol and to phenylephrine, but drug-elicited cAMP and inositol phosphate production did not differ between sexes. The results demonstrate sex-related differences in atrial function that can be partially explained by greater myofibrillar Ca2+-sensitivity in females. A potential contribution of sarcolemmal Ca2+ influx is suggested by greater tetanic contraction in ryanodine-treated female atrium. The larger response of males to adrenergic stimulation does not appear to be explained by higher production of relevant second messengers. Future studies will investigate the role of sex hormones in these sexually dimorphic responses and may indicate a need for gender-specific therapeutic interventions for myocardial dysfunction.
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References
Dahlberg ST: Gender differences in the risk factors for sudden cardiac death. Cardiology 77 (Suppl 2): 31–40, 1990
Kannel WB, Belanger AJ: Epidemiology of heart failure. Am Heart J 121: 951–957, 1991
Echeverria HH, Bilsker MS, Myerberg RJ, Kessler KM: Congestive heart failure: Echocardiographic insights. Am J Med 75: 750–755, 1983
Carroll JD, Carroll EP, Feldman T, Ward DM, Lang RM, McGaughey D, Karp RB: Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation 86: 1099–1107, 1992
Marcus R, Krause L, Weder AB, Dominguez-Mejia AN, Schork D, Julius S: Sex-specific determinants of increased left ventricular mass in the Tecumseh blood pressure study. Circulation 90: 928–936, 1994
Gardin JM, Wagenknecht LE, Anton-Culver H, Flack J, Gidding S, Jurosaki T, Wang ND, Manolio TA: Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. Circulation 92: 380–387, 1995
Merri M, Benhorin J, Alberti A, Locati EH, Moss AJ: Electrocardiographic quantitation of ventricular repolarization. Circulation 80: 1301–1308, 1989
Higgenbotham MB, Morris KG, Coleman RE, Cobb FR: Sex-related differences in the normal cardiac response to upright exercise. Circulation 70: 357–366, 1984
Schaible TF, Scheuer J: Comparison of heart function in male and female rats. Bas Res Cardiol 79: 402–412, 1984
Forman DE, Cittadini A, Azar G, Douglas PS, Wei JY: Cardiac morphology and function in senescent rats: gender-related differences. J Am Coll Cardiol 30: 1972–1877, 1997
Schaible TF, Penparegkul S, Scheuer J: Cardiac responses to exercise training in male and female rats. J Appl Physiol 50: 112–117, 1981
Capasso JM, Remily RM, Smith RH, Sonnenblick EH: Sex differences in myocardial contractility in the rat. Bas Res Cardiol 78: 156–171, 1983
Schwertz DW, Halverson J, Feinberg H, Palmer JW: Alterations in phospholipid metabolism in the globally ischemic rat heart: Emphasis on phosphoinositide specific phospholipase C activity. J Mol Cell Cardiol 19: 685–697, 1987
Terzic A, Vogel S: Amiloride-sensitive actions of an a-adrenoceptor agonist and ouabain in rat atria. Mol Cell Cardiol 22: 391–402, 1990
Pan B-S, Solaro RJ: Calcium binding properties of troponin C in detergent skinned heart muscle fibers. J Biol Chem 626: 7839–7849, 1987
Fabiato A: Computer program for calculation of total from specified free or free from specified total ionic concentration in aqueous solutions containing multiple metals and ligands. Methods Enzymol 157: 378–417, 1988
Pagani ED, Solaro RJ: Methods for measuring functional properties of sarcoplasmic reticulum and myofibrils in small samples of myocardium. In: Arnold Schwartz (ed). Methods in Pharmacology. Vol 5. Plenum Publishing Corp., New York, 1984, pp. 49–61
Carter SG and Karl DW: Inorganic phosphate assay with malachite green: an improvement and evaluation. J Biochem Biophys Methods 7: 7–13, 1982
Piano MR, Rosenblum C, Solaro RJ, Schwertz DW: Calcium sensitivity and the effect of the calcium sensitizing drug pimobendan in the alcoholic myocardium. J Cardiovasc Pharmacol 33: 237–242, 1999
Lowry OH, Roseborough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275, 1951
Piano MR, Schwertz DW: Effect of chronic ethanol exposure on myocardial phosphoinositide turnover. Alcoholism: Clin Exp Res 21: 721–727, 1997
Wreggett KA, Howe LR, Moore JP, Irvine RF: Extraction and recovery of inositol phosphates from tissues. Biochem J 245: 933–934, 1987
Thandroyen FT, McCarthy J, Burton K, Opie LH: Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart. Circ Res 62: 306–314, 1988
Faris EJ: The rat in laboratory investigator. Hafner Publishing Co. NY, 1962, pp 3–4
Kohn D, Barthold SW: Biology and diseases of rats. In: J.G. Fox, B.J. Cohen, F.M. Loew (eds). Laboratory Animal Medicine Academic Press, Inc., New York, 1985, pp 91–122
Brown RA, Filipovich P, Walsh MF, Sowers JR: Influence of sex, diabetes and ethanol on intrinsic contractile performance of isolated rat myocardium. Bas Res Cardiol 91: 353–360, 1996
Grohé C, Kahlert S, Löbbert K, Stimpel M, Karas RH, Vetter H, Neyses L: Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett 416: 107–112, 1997
Grohé C, Kahlert S, Löbbert K, Vetter H: Expression of oestrogen receptor α and β in rat heart: role of local estrogen synthesis. J Endocrinol 156: R1–R7, 1998
Meyer R, Linz KW, Surges R, Meinardus S, Vees J, Hoffmann A, Windholz O, Grohe C: Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat. Exp Physiol 83: 305–321, 1998
Stumpf WE, Sar M, Aumuller G: The heart: A target organ for estradiol. Science 196: 319–321, 1977
Vizgirda V, Schwertz D, Vogel S: Sex differences in adrenergic-stimulated action potentials. J Mol Cell Cardiol 28: 163A, 1996
Vizgirda VM, Schwertz DW, Ziolo MT, Sondgeroth KL, Wahler GM: Sex difference in regulation of the myocardial calcium current. J Mol Cell Cardiol 30: A253, 1998
Rosenkranz-Weiss P, Tomek RJ, Mathew J, Eghbali M: Gender-specific differences in expression of mRNAs for functional proteins in rat ventricular myocardium. J Mol Cell Cardiol 26: 261–270, 1994
Schaible TF, Malhotra A, Caimbrone G: The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats. Circ Res 54: 38–49, 1984
Scheuer J, Malhotra A, Schaible TF, Capasso J: Effects of gonadectomy and hormone replacement on rat hearts. Circ Res 61: 12–19, 1987
Morano I: Effect of sexual hormones on myosin isozyme pattern and left ventricular performance. Acta Cardiol 46: 341–356, 1991
Bers DM, Bassani JW, Bassani RA: Na-Ca exchange and Ca2+ fluxes during contraction and relaxation in mammalian ventricular muscle. Ann NY Acad Sci 779: 430–442, 1996
Jurevicius J, Fischmeister R: cAMP compartmentation is responsible for a local activation of cardiac Ca2+ channels by b-adrenergic agonists. Proc Natl Acad Sci USA 93: 295–299, 1996
Klangkayla B, Chan A: Effects of ovarian hormones on beta-adrenergic and muscarinic receptors in rat heart. Life Sciences 42: 2307–2314, 1988
Johnson BD, Zheng W, Korach KS, Scheuer T, Catterall WA: Increased expression of the cardiac L-type channel in estrogen-deficient mine. J Gen Physiol 110: 135–140, 1997
Patterson E, Lianmin MA, Szabo B, Robinson CP, Thadani U: Ovariectomy and estrogen-induced alterations in myocardial contractility in female rabbits: Role of the L-type calcium channel. J Pharmacol Exp Ther 284: 586–591, 1998
Vizgirda VM, Schwertz DW, Ziolo MT, Wahler GM: Sex differences in beta-adrenergic stimulation of the cardiac calcium current. Circulation 96: I–357, 1997
Terzic A, Puceat M, Vassort G, Vogel S: Cardiac α1-adrenoceptors: An overview. Pharmacol Rev 45: 147–175, 1993
Dubey RK, Gillespie DG, Jackson EK, Keller PJ: 17 Beta-estradiol, its metabolites, and progesterone inhibit cardiac fibroblast growth. Hypertension 31: 522–528, 1998
Bronsaer RP, Grohé C, van Bilsen M, Wellens HJJ, Doevendans PA: 17-β estradiol-induced morphological and transcriptional changes in rat neonatal ventricular cardiomyocytes. J Mol Cell Cardiol 30: A91, 1998.
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Schwertz, D.W., Vizgirda, V., Solaro, R.J. et al. Sexual dimorphism in rat left atrial function and response to adrenergic stimulation. Mol Cell Biochem 200, 143–153 (1999). https://doi.org/10.1023/A:1007011807383
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DOI: https://doi.org/10.1023/A:1007011807383