1,25(OH)2D3 modulates intracellular Ca2+ and force generation in resistance arteries.
The mechanism by which 1 alpha,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances smooth muscle force generation was examined. Rats were injected on three mornings with 1,25(OH)2D3 (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)2D3 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)2D3 = 65.9 +/- 4.0 nM, P < 0.05, n = 24-26 rats). 1,25(OH)2D3 enhanced the active stress and intracellular Ca2+ responses to increasing doses of norepinephrine, and the increases were normalized by verapamil (10 microM). In a second group of animals, 1,25(OH)2D3 significantly increased both basal intracellular Ca2+ and light chain phosphorylation and the active stress and Ca2+ mobilization responses to norepinephrine (10 microM). The hormone did not affect peak or steady-state light chain phosphorylation. Myofilament Ca2+ sensitivity, determined during stimulation with 2 microM norepinephrine, was depressed in vessels isolated from rats treated with 1,25(OH)2D3 [vehicle Ca2+ 50% effective dosé (ED50) = 82.7 +/- 3.8 nM vs. 1,25(OH)2D3 = 104.8 +/- 4.9 nM, P = 0.002]. We conclude that 1,25(OH)2D3 enhances resistance artery force generation by altering smooth muscle Ca2+ homeostasis, with effects on basal and verapamil-sensitive, agonist-induced Ca2+ mobilization.
Bian
K
K
Department of Internal Medicine, University of Texas Medical Branch, Galveston Island 77555-1065, USA.
Ishibashi
K
K
Bukoski
R D
RD
D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000187:drug effects*
D018994:Myosin Light Chains; D002117:Calcitriol