HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/H1296    most recent 00852.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Wu, R. Articles by Wang, P. Search for Related Content PubMed PubMed Citation Articles by Wu, R. Articles by Wang, P.

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

Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, New York 11030

Submitted 10 October 2003 ; accepted in final form 26 April 2004

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.

vasoactive peptide; growth hormone secretagogue receptor; polymicrobial sepsis; aorta; gut

This article has been cited by other articles:

				R. Wu, M. Zhou, P. Das, W. Dong, Y. Ji, D. Yang, M. Miksa, F. Zhang, T. S. Ravikumar, and P. Wang Ghrelin inhibits sympathetic nervous activity in sepsis Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1697 - E1702. [Abstract] [Full Text] [PDF]

				R. Wu, W. Dong, M. Zhou, F. Zhang, C. P. Marini, T. S. Ravikumar, and P. Wang Ghrelin Attenuates Sepsis-induced Acute Lung Injury and Mortality in Rats Am. J. Respir. Crit. Care Med., October 15, 2007; 176(8): 805 - 813. [Abstract] [Full Text] [PDF]

				R. Wu, W. Dong, M. Zhou, X. Cui, H. Hank Simms, and P. Wang Ghrelin improves tissue perfusion in severe sepsis via downregulation of endothelin-1 Cardiovasc Res, November 1, 2005; 68(2): 318 - 326. [Abstract] [Full Text] [PDF]