The small intestine plays an important role in upregulating CGRP during sepsis

Mian Zhou, Angelé J. Arthur, Zheng F. Ba, Irshad H. Chaudry, Ping Wang
2001 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
The small intestine plays an important role in upregulating CGRP during sepsis. Am J Physiol Regulatory Integrative Comp Physiol 280: R382-R388, 2001.-Although studies have indicated that calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide, is upregulated after endotoxic shock, it remains controversial whether this peptide increases during sepsis and, if so, whether the gut is a significant source of CGRP under such conditions. To study this, polymicrobial sepsis was induced
more » ... epsis was induced by cecal ligation and puncture (CLP) followed by fluid resuscitation. Plasma levels of CGRP were measured at 2, 5, and 10 h after CLP (i.e., early, hyperdynamic sepsis) and at 20 h after CLP (late, hypodynamic sepsis). The results indicate that plasma CGRP did not increase at 2-5 h but increased by 177% at 10 h after CLP (P Ͻ 0.05). At 20 h after the onset of sepsis, however, the elevated plasma CGRP returned to the sham level. To determine the source of the increased plasma CGRP, the liver, spleen, small intestine, lungs, and heart were harvested, and tissue CGRP was assayed at 10 h after CLP in additional animals. Only the small intestine showed a significant increase in tissue levels of CGRP (by 129%, P Ͻ 0.05). Determination of portal vs. systemic levels of CGRP indicates that portal CGRP was 65.7 Ϯ 22.7% higher than the systemic level at 10 h after CLP, whereas portal CGRP in sham-operated rats was only 4.9 Ϯ 2.1% higher. Immunohistochemistry examination revealed that CGRP-positive stainings increased in the intestinal tissue but not in the liver at 10 h after the onset of sepsis. The distribution of CGRP stainings was associated with intestinal nerve fibers. These results, taken together, demonstrate that upregulation of CGRP occurs transiently during the progression of sepsis (at the late phase of the hyperdynamic sepsis), and the gut appears to be a major source of such an increase in circulating levels of this peptide. vasoactive peptides; gut; liver; immunohistochemistry; cecal ligation and puncture; hyperdynamic sepsis; calcitonin generelated peptide CALCITONIN GENE-RELATED PEPTIDE (CGRP) is a singlechain polypeptide containing 37 amino acids (6). It is a potent endogenous vasodilatory neuropeptide and a vasoregulatory agent (18). Joyce et al. (17) reported that circulating levels of CGRP increased significantly in patients with sepsis. The increased plasma CGRP
doi:10.1152/ajpregu.2001.280.2.r382 pmid:11208565 fatcat:da34kz3xkbcqtaeassattkeg34