Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following β-Adrenergic Receptor Blockade

James T. Pearson, Nicola Collie, Regis R. Lamberts, Tadakatsu Inagaki, Misa Yoshimoto, Keiji Umetani, Philip Davis, Gerard Wilkins, Pete P. Jones, Mikiyasu Shirai, Daryl O. Schwenke

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4 Citations (Scopus)

Abstract

Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). Whereas b-adrenergic receptor (b-AR) blockers are routinely used for the management of MI, they may also counter b-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 mg/kg, subcutaneously), immediately following the MI or sham surgery. Coronary angiograms were also recorded following b-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 mm) and microvessel recruitment, irrespective of ghrelin treatment. In ghrelin-treated rats, b-AR blockade did not alter the ischemia-induced vasodilation, yet in saline-treated rats, b-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 b-AR blockade treatment for preserving coronary blood flow and cardiac performance in patients who suffer an acute MI.

Original languageEnglish
Pages (from-to)1763-1773
Number of pages11
JournalEndocrinology
Volume159
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018
Externally publishedYes

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