VASCULAR SMOOTH-MUSCLE CELL CALCIUM FLUXES - REGULATION BY ANGIOTENSIN-II AND LIPOPROTEINS

This study examined Ca-45 uptake, Ca-45 efflux, and the distribution of exchangeable Ca-45 in confluent, quiescent cultures of aortic smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). These parameters were investigated under basal conditions and after addition of angiotensin II (Ang II) and low (LDL) and high (HDL) density lipoproteins. Basal Ca-45 uptake was approximately 50% greater in VSMCs from SHRs (p<0.005 versus WKY). Calcium antagonists (diltiazem or nifedipine) abolished this difference. The Ca-45 uptake response to Ang II was approximately twofold greater in SHR than in WKY VSMCs (p < 0.05), and Ang II-induced increments of Ca-45 uptake were weakly inhibited (by approximately 15-25%) by calcium antagonists. Lipoproteins also stimulated Ca-45 uptake in VSMCs, and the apparent affinity of this process was approximately fivefold greater for LDL than for HDL Calcium antagonists did not inhibit either LDL- or HDL-induced Ca-45 uptake. SHR and WKY VSMCs did not differ with respect to Ca-45 uptake induced by either LDL or HDL. The initial size of the slowly exchangeable pool of intracellular Ca2+ was approximately 35% greater in SHR VSMCs (p<0.05 versus WKY). Ang II-induced mobilization of intracellular calcium (measured as the decrease in Ca-45 content of the slowly exchangeable pool) was threefold greater in SHR VSMCs (p<0.005 versus WKY). LDL and HDL marginally stimulated Ca-45 efflux from this pool (less-than-or-equal-to 20% above control) and to comparable extents in both SHR and WKY VSMCs. Enhanced basal Ca2+ uptake and increased stimulation of Ca2+ transport (influx and intracellular mobilization) by Ang II in VSMCs may play a key role in the pathogenesis of hypertension.