The effect of propofol on angiotensin II-induced Ca2+ mobilization in aortic smooth muscle cells from normotensive and hypertensive rats

We studied the effect of propofol (5.6-560 mu mol/L; 1-100 mu g/mL) on the mechanisms involved in Ca2+ mobilization elicited by angiotensin II (AngII) in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. We studie d the variations in intracellular Ca2+ ([Ca2+](i)) concentrations in cultur ed aortic vascular smooth muscle cells (VSMCs) isolated from B-wk-old WKY a nd SHR rats loaded with the Ca2+-sensitive fluorescent dye, Fura-2, using f luorescent imaging microscopy, in the absence of external Ca2+, AngII (1 mu mol/L) induced a transient [Ca2+](i) mobilization from internal stores tha t was larger in SHR than in WKY rats. Ca2+ influx was assessed after extern al Ca2+ (1 mmol/L) reintroduction. Propofol (1-100 mu g/mL) added 5 min bef ore the experiments did not alter AngII-induced Ca2+ release from internal stores in either strain. By contrast, Ca2+ influx elicited by AngII was sig nificantly decreased by propofol. This effect occurred at a smaller concent ration of propofol in the SHR than in the WKY rats. When Ca2+ stores were d epleted by exposure of cells to thapsigargin, an inhibitor of the sarcoendo plasmic reticulum Ca2+-ATPase, reintroduction of Ca2+ to the medium induced a capacitative Ca2+ influx of similar magnitude than that elicited by AngI I. This influx was also significantly decreased by propofol at 100 mu g/mL (WKY: 27 +/- 3% of control values, n = 107; SHR: 16 +/- 3%, n = 47; P < 0.0 01). In conclusion, propofol decreased AngII-induced Ca2+ influx through vo ltage-independent channels, without altering Ca2+ release from internal sto res in aortic VSMCs. The hypertensive rats were found to be more sensitive to the effect of propofol than the normotensive rats. This suggests that th e response of VSMCs to AngII maybe altered by propofol. Implications: In ra t aortic vascular smooth muscle cells, propofol reduced angiotensin II-elic ited Ca2+ entry through capacitative Ca2+ channels without altering Ca2+ re lease from intracellular stores. Spontaneously hypertensive rats were more sensitive to these effects of propofol than normotensive rats. The response of vascular smooth muscle cells to angiotensin II may be altered by propfo l.