ALTERATIONS IN CALCIUM STORES IN AORTIC MYOCYTES FROM SPONTANEOUSLY HYPERTENSIVE RATS

The aim of the present work was to further characterize intracellular calcium stores released by angiotensin II (Ang II) in spontaneously hy pertensive rat (SHR) and Wistar-Kyoto rat (WKY) vascular smooth muscle cells (VSMCs) and to study their alterations associated with prolifer ation. Intracellular Ca2+ concentration was monitored by image analysi s in aortic myocytes loaded with fura 2. In the presence of extracellu lar Ca2+, sensitivity to Ang II in proliferating VSMCs was not differe nt in the two strains, but it increased 10-fold in confluent VSMCs fro m SHR compared with those from WKY. In Ca2+-free medium, Ca2+ release induced by thapsigargin (10 mu mol/L) was significantly greater (about twofold) in SHR than WKY, in both proliferating and confluent culture s, with responses during proliferation being 0.7-fold smaller. Respons es to Ang II were abolished after exposure of the cells to thapsigargi n. In proliferating cultures, ryanodine (10 mu mol/L) did not modify t he rises in intracellular Ca2+ concentration induced by Ang II in VSMC s from both strains. Conversely, in confluent cultures, ryanodine redu ced Ang II (100 nmol/L)-induced Ca2+ release to the same level as in p roliferating cultures, and it suppressed the difference between SHR an d WKY. These results show that the ryanodine-sensitive Ca2+ release in duced by Ang II is enhanced in VSMCs from SHR at confluence and is imp aired during proliferation. Thus, they suggest that differences in Ca2 +-induced Ca2+ release from the sarcoplasmic reticulum may participate in increased responsiveness of VSMCs to Ang II in SHR and in phenotyp ic modulation of vascular myocytes during proliferation.