Disrupted regulation of ghrelin production under antihypertensive treatment in spontaneously hypertensive rats.

ABSTRACT

BACKGROUND: Ghrelin is an acylated peptide hormone mainly secreted from the stomach. When administrated externally it modulates vascular tone mainly through the regulation of autonomic nerve activity. However, the effects of blood pressure (BP) on the production and secretion of ghrelin remain to be clarified. METHODS AND RESULTS: We examined the stomach and plasma levels of ghrelin in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats after a 4-week-intervention with antihypertensive agents (candesartan-cilexetil [ARB], doxazosin [DZN], metoprolol [MP], reserpine [RES]) to clarify the influence of BP on the secretion of ghrelin. The effect of these agents on ghrelin production and secretion were examined by comparing vehicle-treated controls (WKY-Intact, SHR-Intact). Treatment with the 4 antihypertensive drugs all yielded a significant decline in systolic BP in both SHR and WKY. Under these conditions, significantly lower levels of stomach and plasma ghrelin were detected in WKY treated with ARB (P<0.05), DZN (P<0.05), MP (P<0.05) and RES (P<0.05) compared with WKY-Intact, whereas no significant change in the ghrelin levels in the stomach and plasma were detected in SHR under the same treatments. CONCLUSIONS: The findings imply that the production and secretion of ghrelin are controlled by the ambient vascular tone and vice versa in normotensive WKY. This inter-relationship between ghrelin and BP seems to be disrupted in SHR.