Editors' ChoiceCardiovascular Disease

The way to a heart is through the stomach

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Science Translational Medicine  31 Jan 2018:
Vol. 10, Issue 426, eaar7527
DOI: 10.1126/scitranslmed.aar7527

Abstract

Ghrelin maintains coronary artery perfusion following acute myocardial infarction.

Ghrelin, a peptide produced in the intestinal tract, is best known as the “hunger hormone”. Since its discovery in 1999, additional roles for ghrelin have been identified. Ghrelin may improve cardiac function and blunt sympathetic nerve activity, reducing arrhythmias and attenuating remodeling after myocardial infarction (MI). It is not clear if ghrelin can directly modulate coronary artery blood flow or if its vasodilatory actions are entirely mediated through the sympathetic nervous system. It is critical to understand ghrelin’s mechanism of action before considering its use in a clinical setting.

Pearson et al. first investigated ghrelin’s effects on coronary vascular tone following an acute MI in anesthetized rats using microangiography to visualize vessels in vivo. In sham-treated animals, ghrelin infusion caused vasodilation of small coronary arterioles and vasoconstriction of larger arteries. In the acute MI model, treatment with ghrelin preserved greater left ventricular function but there were no differences in coronary perfusion between ghrelin and saline-treated animals, likely due to overwhelming ischemia-induced vasodilation. Next, the investigators used propranolol, a non-selective β-adrenergic receptor blocker, to modulate sympathetic nervous system activity. As expected, the addition of propranolol caused a significant decrease in heart rate, blood pressure, and left ventricular pressure in the acute MI model, with or without ghrelin. In ghrelin-treated rats, the addition of propranolol did not affect blood vessel dilation whereas in saline-treated rats, propranolol blocked ischemia-induced vasodilation of coronary arterioles. Since species-specific effects are possible, ghrelin was also administered to constricted isolated human internal mammary arteries. These arteries were chosen as they are used in surgical coronary artery bypass grafting. Exposure to increasing concentrations of ghrelin resulted in dose-dependent vasodilation in these arteries.

In summary, ghrelin can directly modulate vessel size in a dose-dependent manner. β-adrenergic receptor blockade is standard of care for treatment of MI, but can blunt the ischemia-induced vasodilation of arterioles. Addition of ghrelin preserves ischemia-induced vasodilation, making ghrelin a promising adjuvant therapy to β-adrenergic receptor blockade in acute MI if future clinical trials continue to demonstrate benefit.

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