Agonist-stimulated Ca(2+) transport in mesenteric vascular smooth muscle cells of vitamin D(3)-induced calcium overload rats.
Altered intracellular Ca(2+) homeostasis and accumulated Ca(2+) deposition in arterial walls contribute to the natural arterial aging and aging-related vascular pathologies. To gain further insight into internal relationship between these two factors, a vitamin D(3)-induced vascular Ca(2+) overload rat model was employed. Mesenteric vascular smooth muscle cells (VSMCs) were isolated from both vitamin D(3) and Wistar control rats and were maintained in primary culture for 24 h. Cytosolic and nuclear Ca(2+) ([Ca(2+)](i), [Ca(2+)](n)) in VSMCs were compared between vitamin D(3) and Wistar groups using laser scanning confocal microscopy and Ca(2+)-sensitive-dye Fluo-3. Cytosolic and nuclear Ca(2+) were evaluated under both resting and agonist-stimulated conditions including the voltage-dependent Ca(2+) channel openers BayK8644 and KCl, the inositol-1,4,5-trisphosphate (IP(3))-sensitive Ca(2+) release channel activator IP(3), the ryanodine-sensitive Ca(2+) release channel activator trichloromethane, the sarcoplasmic reticulum Ca(2+) -ATPase inhibitor cyclopiazonic acid, and angiotensin II. Although the levels of [Ca(2+)](n) and [Ca(2+)](i) were comparable between vitamin D(3) and Wistar groups under the resting condition, the increase of [Ca(2+)](n) and [Ca(2+)](i) elicited by various agonists was significantly enhanced in VSMCs from the vitamin D(3) group compared with those from the Wistar group, suggesting abnormality of membrane Ca(2+) gating and intracellular Ca(2+) release under Ca(2+) overload condition. In conclusion, our study indicated that vitamin D(3)-induced vascular Ca(2+) overload may directly interrupt cytosolic and nuclear Ca(2+) homeostasis.
Zhang
Xiaochun
X
Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Wen
Yunyi
Y
Xu
Xiaorong
X
Dong
Feng
F
Ren
Jun
J
D000814:Aniline Compounds; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002762:Cholecalciferol / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008642:Mesenteric Veins / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014966:Xanthenes
D000814:Aniline Compounds; D002120:Calcium Channel Agonists; D005456:Fluorescent Dyes; D014966:Xanthenes; D002762:Cholecalciferol; C059715:Fluo-3; D002118:Calcium