Stimulation of the phosphoinositide signalling system as a possible mechanism for glucocorticoid action in blood pressure control.

Cortisol stimulates the phosphoinositide signalling system in smooth muscle cells of the rat aorta. After stimulation of the cells with cortisol, epinephrine or both compounds, inositol-1,4,5-trisphosphate concentrations were analysed by standardized ion-exchange chromatography procedure. A 15-min stimulation with physiological concentrations of cortisol (0.02-5.0 microgram/ml) led to a dose-dependent increase of the inositol trisphosphate concentrations (up to 500%) and also to a translocation of the calcium- and lipid-dependent protein kinase C activity from the cytosolic to the membranous compartment. Incubation of smooth muscle cells with epinephrine (10(-9) to -5 mol/l) did not lead to an increase in the inositol trisphosphate concentrations. However, after pre-incubation with an average dose of cortisol (0.2 microgram/ml) the inositol trisphosphate response was potentiated by 10(-7) mol/l epinephrine. Our results suggest that stimulation of the phosphoinositide system is a still unknown mechanism of glucocorticoid action in smooth muscle cells, which could influence intracellular free calcium and thus vascular reactivity and blood pressure.