Sexual dimorphism in rat left atrial function and response to adrenergic stimulation

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 m yocardial function and response to adrenergic agonists. Contractile paramet ers were measured in isolated atria by conventional isometric methods in th e 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 gen erated by treating the atrium with ryanodine followed by high frequency sti mulation. Developed force was greater and maximal rates of contraction and relaxation were more rapid in the female atrium. The relationship between C a2+ concentration and force in both intact atria and detergent-skinned atri al fibers in females fell to the left of that for males. At low Ca2+ concen trations, skinned fibers from female atria generated more force and myofibr ils from female atria had higher myosin ATPase activity than males. Tetanic contraction in the presence of high extracellular Ca2+ was greater in fema le atria. Male atrium had larger inotropic responses to isoproterenol and t o phenylephrine, but drug-elicited cAMP and inositol phosphate production d id not differ between sexes. The results demonstrate sex-related difference s in atrial function that can be partially explained by greater myofibrilla r Ca2+-sensitivity in females. A potential contribution of sarcolemmal Ca2 influx is suggested by greater tetanic contraction in ryanodine-treated fe male atrium. The larger response of males to adrenergic stimulation does no t appear to be explained by higher production of relevant second messengers . Future studies will investigate the role of sex hormones in these sexuall y dimorphic responses and may indicate a need for gender-specific therapeut ic interventions for myocardial dysfunction.