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

Abstract

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.

Progressive Decrease in Coronary Vascular Function Associated With Type 2 Diabetic Heart Disease

“…We have previously described the high definition achieved with SR microangiography for visualizing and imaging microvessels of various vascular beds ( Shirai et al, 2013 ), including the coronary circulation ( Pearson et al, 2018 ). One significant limitation with SR is that it is not possible to assess (i) the integrity of the vascular wall for smooth muscle hypertrophy, which would reduce flow, and (ii) changes in the expression of key proteins that regulate vascular tone, such as ROCK and eNOS.…”

“… A schematic diagram showing the experimental set-up for coronary microangiography in an anesthetized mouse model using monochromatic synchrotron radiation at the SPring-8 facilities in Hyogo, Japan (modified from Pearson et al, 2018 ). …”

Ghrelin and vascular protection

“…Callaghan and associates ( 15 ) have reasoned that AG does not directly alter vasomotor tone, since mesenteric and aortic segments did not dilate to AG, but rather AG might evoke hypotension by inhibiting sympathetic afferent activity to release tonic constrictor tone. Nonetheless, we have shown with in vivo microangiography that vessel responses evoked by AG appear to be dependent on vessel size as AG constricted large conduit arteries while dilating arterioles in the same vascular bed in rats following either induction of myocardial infarction or sham procedure ( 16 ). Beta-blockade with propranolol did not significantly alter vessel responses to AG.…”

“…Beta-blockade with propranolol did not significantly alter vessel responses to AG. However, selective GHS-R1a inhibition blocked both dilator and constrictor responses to AG in sham-treated rats ( 16 ). In the same study, AG evoked dose-dependent dilation of human internal mammary arteries.…”

Effect of Tourniquet Use in Ankle Arthroscopic Surgery on Postoperative Recovery: A Prospective Non- Randomized Controlled Study

“…As a response to hypoxia, IMA is a product generated from albumin. Previous studies have de ned IMA as a new marker for ischemic diseases, as its level is markedly rising in acute ischemic conditions, such as myocardial, cerebral and pulmonary ischemia [25,27]. Recently, increasing studies have been focused on the changes of MDA and IMA levels involving use of tourniquet, and found a non-tourniquet technique could reduce the levels and IRI associated side effects following knee arthroscopic surgery [25].…”