Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following β-Adrenergic Receptor Blockade
| Autor: | Daryl O. Schwenke, Philip Davis, Misa Yoshimoto, Tadakatsu Inagaki, Gerard T. Wilkins, Peter P. Jones, Keiji Umetani, Mikiyasu Shirai, James T. Pearson, Regis R. Lamberts, Nicola D. Collie |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Sympathetic Nervous System Vasodilator Agents Adrenergic beta-Antagonists Myocardial Infarction Myocardial Ischemia Ischemia Vasodilation 030204 cardiovascular system & hematology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Endocrinology Left coronary artery Heart Rate medicine.artery Internal medicine medicine Animals Myocardial infarction business.industry medicine.disease Coronary Vessels Propranolol Ghrelin Rats Blockade 030104 developmental biology Microangiography business Perfusion |
| Zdroj: | Endocrinology. 159:1763-1773 |
| ISSN: | 1945-7170 |
| DOI: | 10.1210/en.2017-03070 |
| Popis: | Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). Whereas β-adrenergic receptor (β-AR) blockers are routinely used for the management of MI, they may also counter β-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 µg/kg, subcutaneously), immediately following the MI or sham surgery. Coronary angiograms were also recorded following β-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 µm) and microvessel recruitment, irrespective of ghrelin treatment. In ghrelin-treated rats, β-AR blockade did not alter the ischemia-induced vasodilation, yet in saline-treated rats, β-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 β-AR blockade treatment for preserving coronary blood flow and cardiac performance in patients who suffer an acute MI. |
| Databáze: | OpenAIRE |
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