Department of Pharmacology, University of Mississippi School of Pharmacy and Research Institute of Pharmaceutical Sciences, MS 38677, USA.
Exp Gerontol. 2009 Mar;44(3):201-7. doi: 10.1016/j.exger.2008.10.007. Epub 2008 Nov 5.
Intracellular Ca(2+) signaling is important to perfusion pressure related arterial reactivity and to vascular disorders including hypertension, angina and ischemic stroke. We have recently shown that advancing-age leads to calcium signaling adaptations in mesenteric arterial myocytes from C57 BL/6 mice [Corsso, C.D., Ostrovskaya, O., McAllister, C.E., Murray, K., Hatton, W.J., Gurney, A.M., Spencer, N.J., Wilson, S.M., 2006. Effects of aging on Ca(2+) signaling in murine mesenteric arterial smooth muscle cells. Mech. Ageing Dev. 127, 315-323)] which may contribute to decrements in perfusion pressure related arterial contractility others have shown occur. Even still, the mechanisms underlying the changes in Ca(2+) signaling and arterial reactivity are unresolved. Ca(2+) transport and storage capabilities are thought to contribute to age-related Ca(2+) signaling dysfunctions in other cell types. The present studies were therefore designed to test the hypothesis that cytosolic and compartmental Ca(2+) homeostasis in mesenteric arterial myocytes changes with advanced age. The hypothesis was tested by performing digitalized fluorescence microscopy on mesenteric arterial myocytes isolated from 5- to 6-month and 29- to 30-month-old C57Bl/6 mice. The data provide evidence that with advanced age capacitative Ca(2+) entry and sarcoplasmic reticulum Ca(2+) storage are increased although sarcoplasmic reticulum Ca(2+) uptake and plasma membrane Ca(2+) extrusion are unaltered. Overall, the studies begin to resolve the mechanisms associated with age-related alterations in mesenteric arterial smooth muscle Ca(2+) signaling and their physiological consequences.
细胞内钙离子信号对于与灌注压相关的动脉反应性以及包括高血压、心绞痛和缺血性中风在内的血管紊乱非常重要。我们最近表明,随着年龄的增长,C57BL/6 小鼠的肠系膜动脉平滑肌细胞中的钙信号适应[Corsso,C.D.,Ostrovskaya,O.,McAllister,C.E.,Murray,K.,Hatton,W.J.,Gurney,A.M.,Spencer,N.J.,Wilson,S.M.,2006。衰老对鼠肠系膜动脉平滑肌细胞中 Ca(2+)信号的影响。Mech. Ageing Dev. 127,315-323)]可能导致与灌注压相关的动脉收缩性下降,其他人已经表明这种下降会发生。尽管如此,导致 Ca(2+)信号和动脉反应性变化的机制仍未解决。据认为,Ca(2+)转运和储存能力有助于其他细胞类型与年龄相关的 Ca(2+)信号功能障碍。因此,本研究旨在检验以下假设:即肠系膜动脉平滑肌细胞的细胞质和隔室 Ca(2+)稳态随年龄增长而改变。通过对来自 5-6 个月和 29-30 个月大的 C57Bl/6 小鼠的肠系膜动脉平滑肌细胞进行数字化荧光显微镜检查,对假设进行了测试。数据提供的证据表明,随着年龄的增长,电容性 Ca(2+)内流和肌浆网 Ca(2+)储存增加,而肌浆网 Ca(2+)摄取和质膜 Ca(2+)外排保持不变。总的来说,这些研究开始阐明与肠系膜动脉平滑肌 Ca(2+)信号相关的与年龄相关的变化及其生理后果的机制。