Heart ischemia-reperfusion induces local upregulation of vasoconstrictor endothelin receptor type B in rat coronary arteries downstream of occlusion

TY - JOUR

T1 - Heart ischemia-reperfusion induces local upregulation of vasoconstrictor endothelin receptor type B in rat coronary arteries downstream of occlusion

AU - Skovsted, Gry Freja

AU - Kruse, L.S.

AU - Larsen, R

AU - Pedersen, A F

AU - Trautner, S

AU - Sheykhzade, Majid

AU - Edvinsson, L

N1 - This article is protected by copyright. All rights reserved.

PY - 2014/6

Y1 - 2014/6

N2 - Background and Purpose Endothelins act via two receptor subtypes, ET A and ETB. Under physiological conditions in coronary arteries, ETA receptors expressed in smooth muscle cells mediate vasoconstriction whereas ETB receptors mainly found in endothelial cells mediate vasorelaxation. However, under pathophysiological conditions, ETB receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. Here, we have investigated whether vasoconstrictor ETB receptors are up-regulated in coronary arteries after experimental myocardial ischaemia in rats. Experimental Approach 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 (ETB receptor agonist) and endothelin-1 (with or without ET A or ETB receptor blockade). The distribution of ET B receptors was localized with immunohistochemistry and quantified by Western blot. Key Results Endothelin ETB 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 ETA receptor-mediated vasoconstriction was unaltered in all groups. Conclusions and Implications Ischaemia-reperfusion induced local up-regulation of ETB receptors in the smooth muscle cells of coronary arteries in the post-ischaemic area. In contrast, in non-ischaemic areas, ETB receptor function was unaltered.

AB - Background and Purpose Endothelins act via two receptor subtypes, ET A and ETB. Under physiological conditions in coronary arteries, ETA receptors expressed in smooth muscle cells mediate vasoconstriction whereas ETB receptors mainly found in endothelial cells mediate vasorelaxation. However, under pathophysiological conditions, ETB receptors may also be expressed in vascular smooth muscle cells mediating vasoconstriction. Here, we have investigated whether vasoconstrictor ETB receptors are up-regulated in coronary arteries after experimental myocardial ischaemia in rats. Experimental Approach 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 (ETB receptor agonist) and endothelin-1 (with or without ET A or ETB receptor blockade). The distribution of ET B receptors was localized with immunohistochemistry and quantified by Western blot. Key Results Endothelin ETB 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 ETA receptor-mediated vasoconstriction was unaltered in all groups. Conclusions and Implications Ischaemia-reperfusion induced local up-regulation of ETB receptors in the smooth muscle cells of coronary arteries in the post-ischaemic area. In contrast, in non-ischaemic areas, ETB receptor function was unaltered.

U2 - 10.1111/bph.12606

DO - 10.1111/bph.12606

M3 - Journal article

C2 - 24467585

SN - 0007-1188

VL - 171

SP - 2726

EP - 2738

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

IS - 11

ER -