title: Gene expression and functional activity of sodium/calcium exchanger enhanced in vascular smooth muscle cells of spontaneously hypertensive rats.
abstract: Effects of hypertension on the function of the Na+/Ca2+ exchanger (NCX) were investigated by analyzing vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. Angiotensin II-induced 45Ca2+ efflux from VSMCs mediated by NCX was enhanced by up to 3-fold in SHR compared with WKY, whereas ionomycin-induced Ca efflux mediated by NCX was not different between SHR and WKY. The decline rate from the peak value of intracellular 45Ca2+ concentration ([Ca2+]i) mobilized by angiotensin II was decelerated by removal of extracellular sodium (Na+o) in SHR but not in WKY. Gene expressions of NCX subtype 1 and angiotensin II receptor type1A assessed by quantitative RT-PCR were increased by 1.3- and 1.5-fold, respectively in SHR compared with WKY. NCX protein was also increased 1.6-fold in SHR compared with WKY. MEK inhibitor, PD98059, partly blocked the Nao-dependent acceleration of the [Ca2+]i recovery rate and tyrosine kinase inhibitor, genistein, diminished it in SHR. Genistein decreased angiotensin II-induced Nao- dependent 45Ca2+ efflux. However, angiotensin II did not enhance the tyrosine phosphorylation of NCX. These results suggest that acceleration of Ca2+ efflux from VSMCs of SHR was at least partly due to the enhancement of functional activity of NCX via increased gene expression and tyrosine phosphorylation in connection with hypertension.
authors.affiliation: Department of Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohizumi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Seya
authors.forename: Shigeru
authors.initials: S
authors.lastname: Motomura
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology; D015151:Immunoblotting; D047468:Immunoprecipitation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D047428:Protein Kinase Inhibitors; D044140:Receptor, Angiotensin, Type 1; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D000804:Angiotensin II; D019833:Genistein; D002118:Calcium