Heart failure increased Na/Ca exchanger current and reduced beta-adrenergic responsiveness in male swine myocytes compared to females, an effect eliminated by furosemide therapy.
Does gender modify the effect of heart failure on Na/Ca exchanger current and beta-adrenergic responsiveness in pig myocytes?
Gender-specific differences in calcium handling, specifically a blunted increase in NCX current in females during heart failure, may contribute to their improved survival, though this advantage appears to be eliminated by diuretic therapy.
Clinical trials suggest females experience less heart failure (HF) progression, mortality, and arrhythmia frequency. HF increases Na/Ca exchanger (NCX) expression and activity contributing to both depressed contractility and ventricular arrhythmias, but whether gender modifies this effect is unknown. Left ventricular myocytes were isolated from control and from tachycardic pacing-induced failing swine hearts of both sexes. The Ni-sensitive NCX current (I(NCX)) was measured in voltage clamp after blocking other channels. In control myocytes there is no difference in basal I(NCX) and beta-adrenergic responsiveness between male and female animals. HF greatly increased I(NCX) and reduced beta-adrenergic responsiveness in males compared to females, an effect that was eliminated by PP1. Diuretic therapy (furosemide, 1 mg/kg/day) further enhanced I(NCX) and reduced beta-adrenergic responsiveness in females and eliminated the gender difference. Gender-specific differences in calcium handling may contribute to improved survival of females in HF.
Wei et al. (Thu,) conducted a other in Heart failure. Heart failure (tachycardic pacing-induced) and furosemide vs. Control myocytes; male vs female was evaluated on Ni-sensitive NCX current (I(NCX)) and beta-adrenergic responsiveness. Heart failure increased Na/Ca exchanger current and reduced beta-adrenergic responsiveness in male swine myocytes compared to females, an effect eliminated by furosemide therapy.