Plasma ghrelin and obestatin levels are increased in spontaneously hypertensive rats

Abstract

Obestatin, encoded by the same gene as ghrelin, was first described as a physiological opponent of ghrelin. We investigated fasting plasma ghrelin and obestatin levels in spontaneously hypertensive rats and Wistar-Kyoto rats. We found that ghrelin levels, obestatin levels and the ratio of ghrelin to obestatin were significantly higher in spontaneously hypertensive rats than Wistar-Kyoto rats. Systolic blood pressure and diastolic blood pressure were positively correlated; however, heart period and baroreflex sensitivity were negatively correlated with ghrelin levels. Systolic blood pressure was positively correlated, whereas baroreflex sensitivity was negatively correlated with obestatin levels. In addition, systolic blood pressure was a significantly independent variable of ghrelin levels, obestatin levels, and the ghrelin to obestatin ratio in a multiple regression analysis. Our data suggests that there is a disturbance of ghrelin and obestatin in the circulation of spontaneously hypertensive rats and the ghrelin/obestatin system might play a role in blood pressure regulation.

Introduction

Ghrelin was first identified from rat stomachs, and subsequent studies have shown that ghrelin has a multiplicity of physiological functions such as stimulating appetite, initiating food intake, controlling gastric motility and modulating energy metabolism [5], [14]. In addition, there are some researches demonstrating that ghrelin is intimately correlated with blood pressure. Firstly, Nagaya et al. found that the intravenous injection of ghrelin could decrease peripheral artery resistance, leading to a drop in blood pressure without an increase in heart rate (HR) in healthy volunteers [10]. Secondly, Matsumura et al. also found that the intravenous injection of ghrelin could elicit dose-related decreases in arterial pressure and HR, and intracerebroventricular injection of ghrelin could decrease arterial pressure, HR, and renal sympathetic nerve activity in conscious rabbits [9]. Finally, Makino et al. once found that fasting plasma ghrelin concentration was significantly higher in patients with pregnancy-induced hypertension (PIH) than normal pregnant women [8]. These results suggest that ghrelin may play an important role in blood pressure regulation.

In 2005, Zhang et al. first reported that they found a ghrelin-associated peptide, encoded by the same gene as ghrelin, and named it obestatin [16]. An interesting finding was that obestatin, though derived from the same peptide precursor as ghrelin, suppressed food intake, inhibited jejunal contraction, decreased body weight gain, and antagonized the actions of ghrelin when both peptides were co-administered [16]. In our department, Guo et al. showed that obese individuals would display a disturbance of ghrelin and obestatin levels and suggested that this might play a role in the pathophysiological progress of the disease [4]. Recently, Anderwald-Stadler et al. found that the fasting plasma obestatin level was negatively correlated with SBP in insulin-resistant humans, suggesting a possible role of obestatin in the regulation of blood pressure [2]. To the best of our knowledge, plasma obestatin profiles in relation to ghrelin in hypertension have not been studied. Therefore, the aim of this study was to investigate the fasting plasma ghrelin and obestatin levels and their relationship with blood pressure, HR and the baroreflex function in SHR, the animal model of human essential hypertension [11].