CHARACTERIZATION OF ENHANCED CA-45(2+) EFFLUX IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS

被引：7

作者：

CHEN, S ^{[1
]}

MONTEITH, GR ^{[1
]}

ROUFOGALIS, BD ^{[1
]}

机构：

[1] UNIV SYDNEY,DEPT PHARM,SYDNEY,NSW 2006,AUSTRALIA

来源：

AMERICAN JOURNAL OF HYPERTENSION | 1995年 / 8卷 / 10期

基金：

英国医学研究理事会;

关键词：

SPONTANEOUSLY HYPERTENSIVE RATS; CA2+ EFFLUX; CA2+ PUMP; NA+-CA2+ EXCHANGE; PROTEIN KINASE C; CALCIUM;

D O I：

10.1016/0895-7061(95)00226-X

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

In this study we have compared Ca2+ efflux in cultured aortic smooth muscle cells derived from male, 10-week-old spontaneously hypertensive and Wistar-Kyoto rats. The role of Ca2+-dependent protein kinase C and Ca2+ uptake in the regulation of the Ca2+ pump and Na+-Ca2+ exchange mediated Ca2+ efflux were investigated. Basal, angiotensin II, and ionomycin-stimulated Ca2+ effluxes were significantly higher in spontaneously hypertensive rats. Brief (5 min) or prolonged (3 h) incubation of the cells with 100 nmol/L 12-O-tetradecanoylphorbol-13-O-acetate (TPA), a protein kinase C stimulator, did not significantly affect the maximum Ca2+ efflux rate in either strain. However, the Ca2+ efflux rates at early timepoints in Wistar-Kyoto rats were increased by TPA, but not in spontaneously hypertensive rats. Incubation of cells with [Ca-45]-labeled CaCl, in balanced salt solution for 4 h led to greater Ca uptake in spontaneously hypertensive rats compared to Wistar-Kyoto controls. Verapamil (1 mu mol/for 4 h reduced the cellular Ca content of spontaneously hypertensive rats by 30% to the level of Wistar-Kyoto rats; it also reduced the Ca content in Wistar-Kyoto rats, but to a lesser extent (18%). In parallel, Ca2+ efflux was also reduced by verapamil to a greater extent in spontaneously hypertensive rats than in Wistar-Kyoto rats. We conclude that Ca2+ efflux was enhanced in spontaneously hypertensive rats by a mechanism partly associated with greater Ca2+ uptake by a verapamil-sensitive pathway and possibly an alteration of protein kinase C regulation. However, an up-regulation of the number or efficiency of Ca2+ efflux sites may also significantly contribute as an adaptive response to enhanced Ca2+ influx.

引用

页码：1015 / 1022

页数：8

共 28 条

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