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

Abstract

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.

• Authors: Rongqian Wu, Mian Zhou, Xiaoxuan Cui, H Hank Simms, Ping Wang
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 287 Issue 3 Pg. H1296-302 (Sep 2004) ISSN: 0363-6135 [Print] United States
• PMID: 15155262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ghrelin
• Lipopolysaccharides
• Peptide Hormones
• RNA, Messenger
• Receptors, G-Protein-Coupled
• Receptors, Ghrelin

Topics

• Animals
• Blood Vessels (drug effects, physiopathology)
• Cardiovascular System (metabolism)
• Cecum
• Ghrelin
• Immunohistochemistry
• Intestines (blood supply)
• Ligation
• Lipopolysaccharides (pharmacology)
• Male
• Myocytes, Smooth Muscle (drug effects, metabolism, pathology)
• Peptide Hormones (blood, metabolism)
• Punctures
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Receptors, Ghrelin
• Sepsis (blood, etiology, physiopathology)
• Tissue Distribution
• Up-Regulation