CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
Male and female hypertrophic rat cardiac myocyte functional responses to ischemic stress and β-adrenergic challenge are different.
CLAIRE L. CURL; STEPHEN B. HARRAP; TRISTAN W. HARDING; LEA DELBRIDGE; BELL, JAMES; MARTIN G. VILA PETROFF
Biol Sex Differ
Año: 2016 vol. 7
Background: Cardiac hypertrophy is the most potent cardiovascular risk factor after age, and relative mortalityrisk linked with cardiac hypertrophy is greater in women. Ischemic heart disease is the most common form ofcardiovascular pathology for both men and women, yet significant differences in incidence and outcomes existbetween the sexes. Cardiac hypertrophy and ischemia are frequently occurring dual pathologies. Whether thecellular (cardiomyocyte) mechanisms underlying myocardial damage differ in women and men remains to bedetermined. In this study, utilizing an in vitro experimental approach, our goal was to examine the propositionthat responses of male/female cardiomyocytes to ischemic (and adrenergic) stress may be differentially modulatedby the presence of pre-existing cardiac hypertrophy.Methods: We used a novel normotensive custom-derived hypertrophic heart rat (HHR; vs control strain normalheart rat (NHR)). Cardiomyocyte morphologic and electromechanical functional studies were performed usingmicrofluorimetric techniques involving simulated ischemia/reperfusion protocols.Results: HHR females exhibited pronounced cardiac/cardiomyocyte enlargement, equivalent to males. Underbasal conditions, a lower twitch amplitude in female myocytes was prominent in normal but not in hypertrophicmyocytes. The cardiomyocyte Ca2+ responses to β-adrenergic challenge differed in hypertrophic male and femalecardiomyocytes, with the accentuated response in males abrogated in females?even while contractile responseswere similar. In simulated ischemia, a marked and selective elevation of end-ischemia Ca2+ in normal femalemyocytes was completely suppressed in hypertrophic female myocytes?even though all groups demonstratedsimilar shifts in myocyte contractile performance. After 30 min of simulated reperfusion, the Ca2+ desensitizationcharacterizing the male response was distinctively absent in female cardiomyocytes.