TY - JOUR
T1 - Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol
AU - Chen, Jarvis
AU - Petranka, John
AU - Yamamura, Ken
AU - London, Robert E.
AU - Steenbergen, Charles
AU - Murphy, Elizabeth
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2003/12
Y1 - 2003/12
N2 - Males exhibit enhanced myocardial ischemia-reperfusion injury versus females under hypercontractile conditions associated with increased sarcoplasmic reticulum (SR) Ca2+. We therefore examined whether there were gender differences in SR Ca2+. We used NMR Ca 2+ indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N′ ,N′-tetraacetic acid to measure SR Ca2+ in perfused rabbit hearts. Isoproterenol increased SR Ca2+ in males from a baseline of 1.13 ± 0.07 to 1.52 ± 0.24 mM (P < 0.05). Female hearts had basal SR Ca2+ that was not significantly different from males (1.04 ± 0.03 mM), and addition of isoproterenol to females resulted in a time-averaged SR Ca2+ (0.97 ± 0.07 mM) that was significantly less than in males. To confirm this difference, we measured caffeine-induced release of SR Ca2+ with fura-2 in isolated ventricular myocytes. Ca2+ release after caffeine in untreated male myocytes was 377 ± 41 nM and increased to 650 ± 55 nM in isoproterenol-treated myocytes (P < 0.05). Ca2+ release after caffeine addition in untreated females was 376 ± 27 nM and increased to 503 ± 49 nM with isoproterenol, significantly less than in male myocytes treated with isoproterenol (P < 0.05). Treatment of female myocytes with N G-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), resulted in higher SR Ca2+ release than that measured in females treated only with isoproterenol and was not significantly different from that measured in males with isoproterenol. Female myocytes also have significantly higher levels of neuronal NOS. This gender difference in SR Ca2+ handling may contribute to reduced ischemia-reperfusion injury observed in females.
AB - Males exhibit enhanced myocardial ischemia-reperfusion injury versus females under hypercontractile conditions associated with increased sarcoplasmic reticulum (SR) Ca2+. We therefore examined whether there were gender differences in SR Ca2+. We used NMR Ca 2+ indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N′ ,N′-tetraacetic acid to measure SR Ca2+ in perfused rabbit hearts. Isoproterenol increased SR Ca2+ in males from a baseline of 1.13 ± 0.07 to 1.52 ± 0.24 mM (P < 0.05). Female hearts had basal SR Ca2+ that was not significantly different from males (1.04 ± 0.03 mM), and addition of isoproterenol to females resulted in a time-averaged SR Ca2+ (0.97 ± 0.07 mM) that was significantly less than in males. To confirm this difference, we measured caffeine-induced release of SR Ca2+ with fura-2 in isolated ventricular myocytes. Ca2+ release after caffeine in untreated male myocytes was 377 ± 41 nM and increased to 650 ± 55 nM in isoproterenol-treated myocytes (P < 0.05). Ca2+ release after caffeine addition in untreated females was 376 ± 27 nM and increased to 503 ± 49 nM with isoproterenol, significantly less than in male myocytes treated with isoproterenol (P < 0.05). Treatment of female myocytes with N G-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), resulted in higher SR Ca2+ release than that measured in females treated only with isoproterenol and was not significantly different from that measured in males with isoproterenol. Female myocytes also have significantly higher levels of neuronal NOS. This gender difference in SR Ca2+ handling may contribute to reduced ischemia-reperfusion injury observed in females.
KW - Ischemia
KW - Neuronal nitric oxide synthase
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U2 - 10.1152/ajpheart.00557.2003
DO - 10.1152/ajpheart.00557.2003
M3 - Article
C2 - 12946930
AN - SCOPUS:0344440784
VL - 285
SP - H2657-H2662
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 6 54-6
ER -