Gene expression and functional activity of sodium/calcium exchanger enhanced in vascular smooth muscle cells of spontaneously hypertensive rats.
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.
Taniguchi
Satoshi
S
Department of Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan.
Furukawa
Ken-Ichi
K
Sasamura
Satoshi
S
Ohizumi
Yasushi
Y
Seya
Kazuhiko
K
Motomura
Shigeru
S
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
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