Open AccessGene Expression and Functional Activity of Sodium/Calcium Exchanger Enhanced in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats
Author(s) -
Satoshi Taniguchi,
KenIchi Furukawa,
Satoshi Sasamura,
Yasushi Ohizumi,
Kazuhiko Seya,
Shigeru Motomura
Publication year - 2004
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200405000-00004
Subject(s) - medicine , endocrinology , vascular smooth muscle , angiotensin ii , chemistry , sodium calcium exchanger , phosphorylation , extracellular , efflux , renin–angiotensin system , calcium , intracellular , sodium , receptor , blood pressure , biochemistry , smooth muscle , organic chemistry
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.