Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase of sepsis

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 3; p. H1296
• Main Authors: Wu, Rongqian, Zhou, Mian, Cui, Xiaoxuan, Simms, H Hank, Wang, Ping
• Format: Journal Article
• Language: English
• Published: United States 01-09-2004
• Subjects: Animals; Blood Vessels - drug effects; Blood Vessels - physiopathology; Cardiovascular System - metabolism; Cecum; Ghrelin; Immunohistochemistry; Intestines - blood supply; Ligation; Lipopolysaccharides - pharmacology; Male; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Peptide Hormones - blood; Peptide Hormones - metabolism; Punctures; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Ghrelin; RNA, Messenger - metabolism; Sepsis - blood; Sepsis - etiology; Sepsis - physiopathology; Tissue Distribution; Up-Regulation
• ISSN: 0363-6135
• DOI: 10.1152/ajpheart.00852.2003

Ghrelin, a newly identified endogenous ligand for growth hormone secretagogue receptor 1a (GHSR-1a, i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide. Although sepsis is characterized by an early, hyperdynamic phase, it remains unknown whether ghrelin or GHSR-1a plays a role in the cardiovascular response to sepsis. To determine this, polymicrobial sepsis was induced by cecal ligation and puncture in male adult rats. At 5 h (i.e., early sepsis) or 20 h (i.e., late sepsis) after cecal ligation and puncture, blood and tissue samples were collected. Ghrelin levels and ghrelin and GHSR-1a mRNA expression were assessed by RIA and RT-PCR, respectively. In addition, GHSR-1a protein levels in aorta, heart, and small intestine were determined by Western blotting. The vascular response to ghrelin was determined by using an isolated gut preparation. A primary rat aortic smooth muscle cell culture was used to determine the effects of LPS on GHSR-1a expression. The results indicate that although ghrelin levels decreased at early and late sepsis, its receptor was markedly elevated in early sepsis. Moreover, ghrelin-induced relaxation in resistance blood vessels of the isolated small intestine increased significantly during early sepsis but was not altered in late sepsis. Furthermore, GHSR-1a expression in smooth muscle cells was significantly increased at mRNA and protein levels with stimulation by LPS at 10 ng/ml. These results demonstrate that GHSR-1a expression is upregulated and vascular sensitivity to ghrelin stimulation is increased in the hyperdynamic phase of sepsis.