title: Role of ET-1 receptor binding and [Ca(2+)](i) in contraction of coronary arteries from DOCA-salt hypertensive rats.
abstract: Hypertension is associated with an increase in coronary artery disease, but little is known about the regulation of coronary vascular tone by endothelin-1 (ET-1) in hypertension. The present study evaluated the mechanisms mediating altered contraction to ET-1 in coronary small arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. DOCA-salt rats exhibited an increase in systolic blood pressure and plasma ET-1 levels compared with placebo rats. Contraction to ET-1 (1 x 10(-11) to 3 x 10(-8) M), measured in isolated coronary small arteries maintained at a constant intraluminal pressure of 40 mmHg, was largely reduced in vessels from DOCA-salt rats compared with placebo rats. To determine the role of endothelin receptor binding in the impaired contraction to ET-1, (125)I-labeled ET-1 receptor binding was measured in membranes isolated from coronary small arteries. Maximum binding (fmol/mg protein) and binding affinity were similar in coronary membranes from DOCA-salt rats compared with placebo rats. Changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in freshly dissociated coronary small artery smooth muscle cells loaded with fura 2. ET-1 (10(-9) M) produced a 30 +/- 9% increase in [Ca(2+)](i) in smooth muscle cells from placebo rats, but had no effect on cells from DOCA-salt rats (2 +/- 2%). In summary, the ET-1-induced coronary artery contraction and increase in [Ca(2+)](i) are impaired in DOCA-salt hypertensive rats, whereas endothelin receptor binding is not altered. These results suggest endothelin receptor uncoupling from signaling mechanisms and indicate that impaired [Ca(2+)](i) signaling contributes to the decrease in ET-1-induced contraction of coronary small arteries in DOCA-salt hypertensive rats.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912-2500, USA.
authors.forename: Ararat D
authors.initials: AD
authors.lastname: Giulumian
authors.forename: Mariela M
authors.initials: MM
authors.lastname: Molero
authors.forename: Vikram B
authors.initials: VB
authors.lastname: Reddy
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pollock
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003331:Coronary Vessels / Q000503:physiopathology; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007457:Iodine Radioisotopes; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010919:Placebos; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism*; D015398:Signal Transduction; D012965:Sodium Chloride
chemical_list: D019332:Endothelin-1; D007457:Iodine Radioisotopes; D010919:Placebos; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D002118:Calcium