Alterations in Calcium Stores in Aortic Myocytes From Spontaneously Hypertensive Rats

Abstract

Abstract The aim of the present work was to further characterize intracellular calcium stores released by angiotensin II (Ang II) in spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) vascular smooth muscle cells (VSMCs) and to study their alterations associated with proliferation. Intracellular Ca 2+ concentration was monitored by image analysis in aortic myocytes loaded with fura 2. In the presence of extracellular Ca 2+ , sensitivity to Ang II in proliferating VSMCs was not different in the two strains, but it increased 10-fold in confluent VSMCs from SHR compared with those from WKY. In Ca 2+ -free medium, Ca 2+ release induced by thapsigargin (10 μmol/L) was significantly greater (about twofold) in SHR than WKY, in both proliferating and confluent cultures, with responses during proliferation being 0.7-fold smaller. Responses to Ang II were abolished after exposure of the cells to thapsigargin. In proliferating cultures, ryanodine (10 μmol/L) did not modify the rises in intracellular Ca 2+ concentration induced by Ang II in VSMCs from both strains. Conversely, in confluent cultures, ryanodine reduced Ang II (100 nmol/L)–induced Ca 2+ release to the same level as in proliferating cultures, and it suppressed the difference between SHR and WKY. These results show that the ryanodine-sensitive Ca 2+ release induced by Ang II is enhanced in VSMCs from SHR at confluence and is impaired dur-ing proliferation. Thus, they suggest that differences in Ca 2+ -induced Ca 2+ release from the sarcoplasmic reticulum may participate in increased responsiveness of VSMCs to Ang II in SHR and in phenotypic modulation of vascular myocytes during proliferation.