Previous studies from this laboratory have demonstrated that Na-K-Cl cotransport of vascular smooth muscle cells is inhibited by hormones that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels (e.g., catecholamines) and is stimulated by hormones that increase intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels (e.g., atrial natriuretic peptides). Others have suggested that calcium may also modulate Na-K-Cl cotransport of vascular smooth muscle cells. The goal of the present study was to characterize the mechanism of angiotensin II stimulation of Na-K-Cl cotransport of early passage cultured vascular smooth muscle cells. We found that when vascular smooth muscle cells were treated with angiotensin II or a calcium ionophore, Na-K-Cl cotransport was markedly enhanced above basal levels. We found that when calcium influx was blocked with the calcium chelator EDTA or with three different chemical types of calcium-channel blockers, the stimulatory effects of angiotensin II on Na-K-Cl cotransport were markedly inhibited. Furthermore, when intracellular calcium mobilization was blocked with high concentrations of the calcium chelator quin2 or with the intracellular calcium antagonist 8-(diethyl-amino)octyl 3,4,5-trimethoxybenzoate (TMB-8), the stimulatory effects of angiotensin II on Na-K-Cl cotransport were also substantially inhibited. These results suggest that both calcium influx via receptor-operated calcium channels and intracellular calcium mobilization may play a role in stimulation of Na-K-Cl cotransport of vascular smooth muscle cells in response to angiotensin II.
Effects of Ghrelin on the Intracellular Calcium Concentration in Rat Aorta Vascular Smooth Muscle Cells
