Heart ischaemia–reperfusion induces local up‐regulation of vasoconstrictor endothelin ETB receptors in rat coronary arteries downstream of occlusion. (June 2014)

• Record Type: Journal Article
• Authors: Skovsted, G F; Kruse, L S; Larsen, R; Pedersen, A F; Trautner, S; Sheykhzade, M; Edvinsson, L
• Is Part Of: British journal of pharmacology. Volume 171:Number 11(2014:Jun.)
• Page Start: 2726
• Page End: 2738
• Publication Date: 2014-06
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12606
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12606-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Endothelins act via two receptor subtypes, ET<sub>A</sub> and ET<sub>B</sub>. Under physiological conditions in coronary arteries, ET<sub>A</sub> receptors expressed in smooth muscle cells mediate vasoconstriction whereas ET<sub>B</sub> receptors mainly found in endothelial cells mediate vasorelaxation. However, under pathophysiological conditions, ET<sub>B</sub> receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. Here, we have investigated whether vasoconstrictor ET<sub>B</sub> receptors are up‐regulated in coronary arteries after experimental myocardial ischaemia in rats.</p> </sec> <sec id="bph12606-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Male Sprague‐Dawley rats were subjected to either heart ischaemia–reperfusion (15 min ischaemia and 22 h reperfusion), permanent ischaemia (22 h) by ligation of the left anterior descending coronary artery, or sham operation. Using wire myography, the endothelin receptor subtypes mediating vasoconstriction were examined in isolated segments of the left anterior descending and the non‐ligated septal coronary arteries. Endothelin receptor‐mediated vasoconstriction was examined with cumulative administration of sarafotoxin 6c (ET<sub>B</sub> receptor agonist) and endothelin‐1 (with or without ET<sub>A</sub> or ET<sub>B</sub> receptor blockade). The distribution of ET<sub>B</sub> receptors was localized with immunohistochemistry and quantified by Western blot.</p> </sec> <sec id="bph12606-sec-0003" sec-type="section"> <title>Key Results</title> <p>Endothelin ET<sub>B</sub> receptor‐mediated vasoconstriction and receptor protein levels were significantly augmented in coronary arteries situated downstream of the occlusion after ischaemia–reperfusion compared with non‐ischaemic arteries. In contrast, the ET<sub>A</sub> receptor‐mediated vasoconstriction was unaltered in all groups.</p> </sec> <sec id="bph12606-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Ischaemia–reperfusion induced local up‐regulation of ET<sub>B</sub> receptors in the smooth muscle cells of coronary arteries in the post‐ischaemic area. In contrast, in non‐ischaemic areas, ET<sub>B</sub> receptor function was unaltered.</p> </sec> </abstract>