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Sex Differences in Renal and Cardiovascular Function: Physiology and Pathophysiology

Sex-based differences in myocardial contractile reserve

¹Department of Physiology and the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania; ²Cardiovascular Institute, ³Department of Physiology, and ⁴Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and ⁵Biology Department, Ursinus College, Collegeville, Pennsylvania

Submitted 31 May 2006 ; accepted in final form 20 September 2006

Recent studies have identified sex differences in heart function that may affect the risk of developing heart failure. We hypothesized that there are fundamental differences in calcium (Ca) regulation in cardiac myocytes of males and premenopausal females. Isometric force transients (n = 45) were measured at various stimulation frequencies to define the force frequency responses (FFR) (0.5, 1.0, 1.5, and 2.0 Hz) during either changes in bath Ca ([Ca]_o) (1.0, 1.75, 3.5, and 7.0 mM) or length-tension (20, 40, 60, 80, and 100% L_max) in right ventricle trabeculae from normal male (MT) and premenopausal female (FT) cats. Force-Ca measurements were also obtained in chemically skinned trabeculae. Under basal conditions (0.5 Hz, 1.75 mM Ca, 80% L_max) both MT and FT achieved similar developed forces (DF) (MT 11 ± 1, FT = 10 ± 1 mN/mm²). At low rates and lengths, there is no sex difference. At higher preloads and rates, there is a separation in DF in MT and FT. At basal [Ca]_o both MT and FT exhibited positive FFR (2.0 Hz, 1.75 mM Ca: MT 38 ± 3, FT 21 ± 4 mN/mm²); however, at higher [Ca]_o, MT achieved greater DF (2.0 Hz, 7.0 mM Ca: MT 40 ± 3 and FT = 24 ± 4 mN/mm²). We detected no sex difference in myofilament Ca sensitivity at a sarcomere length of 2.1 µm. However, rapid cooling contractures indicated greater sarcoplasmic reticulum (SR) Ca load in MT at higher frequencies. Despite virtually identical contractile performance under basal conditions, significant sex differences emerge under conditions of increased physiological stress. Given the lack of sex differences in myofilament Ca sensitivity, these studies suggest fundamental sex differences in cellular Ca regulation to achieve contractile reserve, with myocardium from males exhibiting higher SR Ca load.

myocardium; force-frequency response; length-tension relationship; myofilament calcium sensitivity; sarcoplasmic reticulum calcium load

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