Upregulation of cardiovascular ghrelin receptor occurs in the hyperdynamic phase of sepsis.
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.
Wu
Rongqian
R
Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, New York 11030, USA.
Zhou
Mian
M
Cui
Xiaoxuan
X
Simms
H Hank
HH
Wang
Ping
P
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism*; D002432:Cecum; D054439:Ghrelin; D007150:Immunohistochemistry; D007422:Intestines / Q000098:blood supply; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism; D011677:Punctures; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D054440:Receptors, Ghrelin; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D014018:Tissue Distribution; D015854:Up-Regulation
D054439:Ghrelin; D008070:Lipopolysaccharides; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin