Characterization of enhanced 45Ca2+ efflux in cultured vascular smooth muscle cells from spontaneously hypertensive rats.

Abstract:

: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 Ca(2+)-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 [45Ca]-labeled CaCl2 in balanced salt solution for 4 h led to greater Ca uptake in spontaneously hypertensive rats compared to Wistar-Kyoto controls. Verapamil (1 mumol/L) 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.

journal_name

Am J Hypertens

authors

Chen S,Monteith GR,Roufogalis BD

doi

10.1016/0895-7061(95)00226-X

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

1015-22

issue

10 Pt 1

eissn

0895-7061

issn

1941-7225

pii

0895-7061(95)00226-X

journal_volume

8

pub_type

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