Cross Heather R, Murphy Elizabeth, Steenbergen Charles
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H481-9. doi: 10.1152/ajpheart.00790.2001.
To compare ischemia-reperfusion injury in males versus females under hypercontractile conditions, perfused hearts from 129J mice pretreated with 3 mmol/l Ca(2+) or 10(-8) mol/l isoproterenol +/- 10(-6) mol/l N(omega)-nitro-L-arginine methyl ester (L-NAME) were subjected to 20 min of ischemia and 40 min of reperfusion while (31)P NMR spectra were acquired. Basal contractility increased equivalently in female versus male hearts with isoproterenol- or Ca(2+) treatment. Injury was equivalent in untreated male versus female hearts but was greater in isoproterenol or Ca(2+)-treated male than female hearts, as indicated by lower postischemic contractile function, ATP, and PCr. Endothelial nitric oxide (NO) synthase (eNOS) expression was higher in female than male hearts, neuronal NOS (nNOS) did not differ, and inducible NOS (iNOS) was undetectable. Ischemic NO production was higher in female than male hearts, and L-NAME increased injury in female isoproterenol-treated hearts. In summary, isoproterenol or high Ca(2+) pretreatment increased ischemia-reperfusion injury in males more than females. eNOS expression and NO production were higher in female than male hearts, and L-NAME blocked female protection. Females were therefore protected from the detrimental effects of adrenergic stimulation and Ca(2+) loading via a NOS-mediated mechanism.
为了比较在高收缩状态下雄性和雌性小鼠的缺血再灌注损伤，对用3 mmol/l Ca(2+)或10(-8) mol/l异丙肾上腺素+/- 10(-6) mol/l N(ω)-硝基-L-精氨酸甲酯（L-NAME）预处理的129J小鼠的灌注心脏进行20分钟缺血和40分钟再灌注，同时采集(31)P NMR光谱。用异丙肾上腺素或Ca(2+)处理后，雌性和雄性心脏的基础收缩力同等增加。未处理的雄性和雌性心脏的损伤相当，但用异丙肾上腺素或Ca(2+)处理的雄性心脏比雌性心脏的损伤更大，这表现为缺血后收缩功能、ATP和磷酸肌酸（PCr）较低。雌性心脏中内皮型一氧化氮（NO）合酶（eNOS）的表达高于雄性，神经元型NOS（nNOS）无差异，且未检测到诱导型NOS（iNOS）。雌性心脏缺血时的NO生成高于雄性，L-NAME增加了雌性异丙肾上腺素处理心脏的损伤。总之，异丙肾上腺素或高Ca(2+)预处理使雄性小鼠的缺血再灌注损伤比雌性更严重。雌性心脏中eNOS的表达和NO生成高于雄性，L-NAME阻断了雌性的保护作用。因此，雌性通过NOS介导的机制免受肾上腺素能刺激和Ca(2+)负荷的有害影响。
