1,25(OH)(2)D-3 modulates intracellular Ca2+ and force generation in resistance arteries

The mechanism by which 1 alpha,25-dihydroxycholecalciferol [1,25(OH)(2)D-3] enhances smooth muscle force generation was examined. Rats were injected on three mornings with 1,25(OH)(2)D-3 (35 ng/100 g) or vehicle, and on the fourth morning mesenteric resistance arteries were isolated and used for simultaneous measurement of intracellular Ca2+ and force or myosin light chain phosphorylation. 1,25(OH)(2)D-3 did not affect media thickness or wall-to-lumen ratio, but it increased basal intracellular Ca2+ (vehicle = 49.2 +/- 2.2 nM vs. 1,25(OH)(2)D-3 = 65.9 +/- 4.0 nM, P < 0.05, n = 24-26 rats). 1,25(OH)(2)D-3 enhanced the active stress and intracellular Ca2+ responses to increasing doses of norepinephrine, and the increases were normalized by verapamil (10 mu M). In a second group of animals, 1,25(OH)(2)D-3 significantly increased both basal intracellular Ca2+ and light chain phosphorylation and the active stress and Ca2+ mobilization responses to norepinephrine (10 mu M). The hormone did not affect peak or steady-state light chain phosphorylation. Myofilament Ca2+ sensitivity, determined during stimulation with 2 mu M norepinephrine, was depressed in vessels isolated from rats treated with 1,25(OH)(2)D-3 [vehicle Ca2+ 50% effective dose (ED50) = 82.7 +/- 3.8 nM vs. 1,25(OH)(2)D-3 = 104.8 +/- 4.9 nM, P = 0.002]. We conclude that 1,25(OH)(2)D-3 enhances resistance artery force generation by altering smooth muscle Ca2+ homeostasis, with effects on basal and verapamil-sensitive, agonist-induced Ca2+ mobilization.