151. 1,25(OH)2D3 modulates intracellular Ca2+ and force generation in resistance arteries
- Author
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K. Ishibashi, Ka Bian, and Richard D. Bukoski
- Subjects
Male ,medicine.medical_specialty ,Myosin Light Chains ,Myosin light-chain kinase ,Physiology ,chemistry.chemical_element ,Stimulation ,In Vitro Techniques ,Calcium ,Biology ,Muscle, Smooth, Vascular ,Norepinephrine (medication) ,Calcitriol ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Phosphorylation ,Rats, Wistar ,Arteries ,Rats ,Endocrinology ,chemistry ,Vasoconstriction ,Verapamil ,Stress, Mechanical ,Cardiology and Cardiovascular Medicine ,Intracellular ,Homeostasis ,medicine.drug - Abstract
The mechanism by which 1α,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 Ca 2+ 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 Ca 2+ (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 Ca 2+ responses to increasing doses of norepinephrine, and the increases were normalized by verapamil (10 μM). In a second group of animals, 1,25(OH) 2 D 3 significantly increased both basal intracellular Ca 2+ and light chain phosphorylation and the active stress and Ca 2+ mobilization responses to norepinephrine (10 μM). The hormone did not affect peak or steady-state light chain phosphorylation. Myofilament Ca 2+ sensitivity, determined during stimulation with 2 μM norepinephrine, was depressed in vessels isolated from rats treated with 1,25(OH) 2 D 3 [vehicle Ca 2+ 50% effective dose (ED 50 ) = 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 Ca 2+ homeostasis, with effects on basal and verapamil-sensitive, agonist-induced Ca 2+ mobilization.
- Published
- 1996
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