title: Mechanism of angiotensin II stimulation of Na-K-Cl cotransport of vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Department of Biological Chemistry and Structure, University of Health Sciences, Chicago Medical School, Illinois 60064.
authors.forename: N E
authors.initials: NE
authors.lastname: Owen
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters
chemical_list: D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D002712:Chlorides; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D000804:Angiotensin II; D000001:Calcimycin; D004533:Egtazic Acid; D015759:Ionomycin; D012964:Sodium; D011188:Potassium