Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion

Abstract

We administered ghrelin, a novel growth hormone-releasing hormone, to isolated perfused rat hearts, coronary arterioles, and cultured neonatal cardiomyocytes to determine its effects on coronary vascular tone, contractility, and natriuretic peptide secretion and gene expression. We also determined cardiac levels of ghrelin and whether the heart is a source of the circulating peptide. Ghrelin dose dependently increased coronary perfusion pressure (44 +/- 9%, P < 0.01), constricted isolated coronary arterioles (12 +/- 2%, P < 0.05), and significantly enhanced the pressure-induced myogenic tone of arterioles. These effects were blocked by diltiazem, an L-type Ca(2+) channel blocker, and bisindolylmaleimide (Bis), a protein kinase C (PKC) inhibitor. Interestingly, coinfusion of ghrelin with diltiazem completely restored myocardial contractile function that was decreased 30 +/- 3% (P < 0.01) by diltiazem alone. In contrast, combination of ghrelin with diltiazem or Bis did not significantly alter atrial natriuretic peptide (ANP) secretion, which was decreased 40% (P < 0.01) and 50% (P < 0.05) by these agents alone, respectively. Administration of ghrelin to cultured cardiomyocytes had no effect on ANP or B-type natriuretic peptide secretion or gene expression. Detectable amounts of low-molecular-weight ghrelin were present in cardiac tissue extracts but not in isolated heart perfusate. Thus we provide the first evidence that ghrelin has a coronary vasoconstrictor action that is dependent on Ca(2+) and PKC. Furthermore, the data obtained from diltiazem infusion suggest that ghrelin has a role in regulation of contractility when L-type Ca(2+) channels are blocked. Finally, the observation that immunoreactive ghrelin is found in cardiac tissue suggests the presence of a local cardiac ghrelin system.

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Ghrelin unexpectedly increased coronary perfusion pressure and constricted isolated coronary arterioles in rats (Pemberton et al, 2004), whereas intracoronary acyl ghrelin infusion unexpectedly decreased coronary blood flow in anesthetized pigs (Grossini et al, 2007). The mechanisms were shown to involve L-type Ca 2ϩ channel and protein kinase C activation (Pemberton et al, 2004) and the inhibition of a tonic coronary ␤ 2 -adrenergic receptor-mediated vasodilatory effect related to the release of nitric oxide (Grossini et al, 2007).…”

Ghrelin, des-acyl ghrelin and obestatin: Three pieces of the same puzzle

“…Indeed, intravenous administration of ghrelin in humans causes a significant decrease in mean arterial pressure, but does not change heart rate [106]. By contrast, ghrelin increases coronary perfusion pressure in rat hearts perfused using the Langendorf system and significantly increases pressure-induced myogenic tone in coronary arterioles [117]. In the microcirculation, ghrelin increases vascular flow, and this action may affect other physiological functions of ghrelin [145].…”

Ghrelin reduces myocardial injury following global ischemia and reperfusion via suppression of myocardial inflammatory response

“…In vitro a study, ghrelin has shown to prevent against the cardiotoxicity of adriamycin may be attributed to up regulation of TNF-α/NF-κB pathways, as well as its mitochondrial stabilization properties [16]. A study reported that, in anesthetized pigs, intracoronary infusion of ghrelin induced coronary artery contraction, thereby reducing coronary circulation and the mechanism of this response has been shown to involve the  To determine if anti-inflammatory mechanisms are involved we planned to measure tissue levels of the known pro-inflammatory mediators (MCP-1, IL-1β, IL-6, and VCAM-1).…”