期刊
ENDOCRINOLOGY
卷 159, 期 4, 页码 1763-1773出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/en.2017-03070
关键词
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资金
- Japan Society for the Promotion of Science
- National Cerebral and Cardiovascular Center Research Institute [25-3-1]
- Department of Physiology, Otago University, New Zealand
Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). Whereas beta-adrenergic receptor (beta-AR) blockers are routinely used for the management of MI, they may also counter beta-AR-mediated vasodilation of coronary vessels. We have reported that ghrelin prevents sympathetic activation following MI. Whether ghrelin modulates coronary vascular tone following MI, either through the modulation of SNA or directly as a vasoactive mediator, has never been addressed. We used synchrotron microangiography to image coronary perfusion and vessel internal diameter (ID) in anesthetized Sprague-Dawley rats, before and then again 30 minutes after induction of an MI (left coronary artery ligation). Rats were injected with either saline or ghrelin (150 mu g/kg, subcutaneously), immediately following the MI or sham surgery. Coronary angiograms were also recorded following beta-AR blockade (propranolol, 2 mg/kg, intravenously). Finally, wire myography was used to assess the effect of ghrelin on vascular tone in isolated human internal mammary arteries (IMAs). Acute MI enhanced coronary perfusion to nonischemicregions through dilation of small arterioles (ID 50 to 250 mu m) and microvessel recruitment, irrespective of ghrelin treatment. In ghrelin-treated rats, beta-AR blockade did not alter the ischemia-induced vasodilation, yet in saline-treated rats, beta-AR blockade abolished the vasodilation of small arterioles. Finally, ghrelin caused a dose-dependent vasodilation of IMA rings (preconstricted with phenylephrine). In summary, this study highlights ghrelin as a promising adjunct therapy that can be used in combination with routine beta-AR blockade treatment for preserving coronary blood flow and cardiac performance in patients who suffer an acute MI.
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