Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat

Abstract

Ghrelin is a gut-brain peptide and its endocrine activities are mediated by GH secretagogue receptor (GHSR)-1a. Des-acyl ghrelin does not activate GHSR-1a and is devoid of endocrine activities. While the microinjection of ghrelin into rat nucleus tractus solitarii (NTS) elicited hypotensive effects, this was not the case upon injection into GHSR-expressing rostral ventrolateral medulla or caudal ventrolateral medulla. To make clear the reason of the discrepancy between receptor distribution and neuronal responses, we examined the cardiovascular response of rats microinjected with des-acyl ghrelin into NTS. Intra-NTS injection of des-acyl ghrelin significantly reduced mean arterial pressure and heart rate. The hypotensive and bradycardic activity evoked by des-acyl ghrelin was not significantly different from that of native ghrelin. These results suggest that des-acyl ghrelin contribute to the regulation of cardiovascular control and that a receptor other than GHSR-1a exists in NTS.

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

“…These direct vasodilatory effects were through endothelium-independent, antagonizing in vitro vasoconstrictory action of endothelin-1 (Wiley and Davenport, 2002) and in vivo GH/IGF-1/nitric oxideindependent mechanisms. Microinjection of both acyl and des-acyl ghrelin in the nucleus tractus solitarii decreases blood pressure in rats Tsubota et al, 2005). Subcutaneous injection of acyl ghrelin attenuated the progression of long-term hypoxia-induced pulmonary hypertension in rats involving down-regulation of endothelin-1 and prevention of impaired NO-mediated vasodilation and thickened wallto-lumen ratio in peripheral pulmonary arteries (Schwenke et al, 2008b).…”

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

“…In the systemic circulation, ghrelin has a vasodilatory effect that is endothelium-independent [82,149] and involves peripheral and central mechanisms [95]. Indeed, intravenous administration of ghrelin in humans causes a significant decrease in mean arterial pressure, but does not change heart rate [106].…”

“…Compared with ghrelin, des-acyl ghrelin shows similar endothelium independent vasodilator potency [82,149]. Like ghrelin, des-acyl ghrelin decreases inotropism [10], inhibits apoptosis of cardiomyocytes [4] and has cardioprotective effects on myocardial injury induced by isoproterenol in rats [92].…”

Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease

“…(9,11). Data in the animal and in the human have described activity of octanoylated ghrelin and des-octanoylated ghrelin in the cardiovascular system (14)(15)(16)(17), but in term of ischaemic heart disease the "active" form may be more physiologically crucial.…”