Gene expression and functional activity of sodium/calcium exchanger enhanced in vascular smooth muscle cells of spontaneously hypertensive rats

• Published in: Journal of cardiovascular pharmacology Vol. 43; no. 5; p. 629
• Main Authors: Taniguchi, Satoshi, Furukawa, Ken-Ichi, Sasamura, Satoshi, Ohizumi, Yasushi, Seya, Kazuhiko, Motomura, Shigeru
• Format: Journal Article
• Language: English
• Published: United States 01.05.2004
• Subjects: Angiotensin II - pharmacology; Animals; Aorta - cytology; Calcium - metabolism; Cells, Cultured; Gene Expression; Genistein - pharmacology; Immunoblotting; Immunoprecipitation; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Angiotensin, Type 1 - biosynthesis; Receptor, Angiotensin, Type 1 - genetics; Reverse Transcriptase Polymerase Chain Reaction; Sodium-Calcium Exchanger - biosynthesis; Sodium-Calcium Exchanger - genetics
• ISSN: 0160-2446
• DOI: 10.1097/00005344-200405000-00004

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.