Aging and Ca2+ signaling in murine mesenteric arterial myocytes

Vascular reactivity may be reduced in old individuals and the (Ca2+)i is important to smooth muscle contractility. Experiments were therefore performed to determine if Ca2+ signaling is altered in mesenteric arterial smooth muscle cells (MASMCs) from 5-6 (young (Y)) and 29-30 month (old (O)) C57bl/6 mice. (Ca2+)i was measured using fura-2 imaging of individual MASMCs. The basal (Ca2+)i of MASMCs from Y (36+/-6 nM n=48) and O (51+/-4 nM n=101) were not significantly different. Total cytosolic Ca2+ (CaT) released by 30s 10 mM caffeine (CAF) or 10 ?M phenylephrine (PE) exposures were estimated by integrating the Ca2+ transient. CaT was proportional to peak (Ca2+)i in both Y and O, but the slope of CaT to peak (Ca2+)i was 2-fold greater in Y for both CAF and PE. The (Ca2+)i increase above basal following SR Ca2+ depletion in Y 66+/-8 nM n=19 was greater than in O 18+/-3 nM n=34. Following store depletion the (Ca2+)i clearance rate (Mclear) with extracellular Ca2+ removal in Y 0.0073+/-0.0009 s-1 n=19 was slower than in O 0.0161+/-0.0008 s-1 n=34. The (Ca2+)i cleared from the cytosol (Mclear*CaT) was proportional to the peak (Ca2+)i and was the same between Y and O for CAF, while that due to PE was greater in O. Aging modifies agonist-induced cytosolic Ca2+ increases and our data imply that altered cytosolic Ca2+ clearance mechanisms are an important component to the Ca2+ signaling impairments. NIH P20 RR15581 from NCRR, AG20400, HL10476, AI55462