title: Chloride-dependent calcium transients induced by angiotensin II in vascular smooth muscle cells.
abstract: Cl- is essential for the vasoconstrictive response to angiotensin II (ANG II). In vascular smooth muscle cells (VSMC), we determined whether ANG II-induced transient increase in intracellular Ca2+ concentration ([Ca2+]i) is Cl- dependent. After incubating the cells at different extracellular Cl- concentration ([Cl-]e) for 40 min, the ANG II-induced Ca2+ transients at 120 meq/l Cl- were more than twice those at either 80 or 20 meq/l Cl-. Replacing Cl- with bicarbonate or gluconate yielded similar results. In addition, after removal of extracellular Ca2+, ANG II-induced as well as platelet-derived growth factor-induced Ca2+ release exhibited Cl- dependency. The difference of Ca2+ release with high vs. low [Cl-]e was not affected by acutely altering [Cl-]e 1 min before administration of ANG II when [Cl-]i was yet to be equilibrated with [Cl-]e. Pretreatment of a Cl- channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid, increased ANG II-induced Ca2+ release and entry at 20 meq/l Cl- but did not alter those at 120 meq/l Cl-. However, after equilibration, a reduced [Cl-]e did not affect thapsigargin-induced Ca2+ release, suggesting that Cl- may not affect the size of intracellular Ca2+ stores. Nevertheless, at high [Cl-], the peak increase of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] induced by ANG II was approximately sixfold that at low [Cl-]. Thus the Cl- -dependent effects of ANG II on Ca2+ transients may be mediated, at least in part, by a Cl- -dependent Ins(1,4,5)P3 accumulation in VSMC.
authors.affiliation: Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC. yhma@mail.cgu.edu.tw
authors.forename: Yunn-Hwa
authors.initials: YH
authors.lastname: Ma
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Wei
authors.forename: Kwan-Hwa
authors.initials: KH
authors.lastname: Su
authors.forename: Harlan E
authors.initials: HE
authors.lastname: Ives
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Morris
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism* / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002118:Calcium