Role of Calcitonin Gene-Related Peptide in Lipopolysaccharide-Induced Septic Shock in Wistar-Kyoto Rats

• Main Authors: Chen Jiun Han, 陳俊翰
• Other Authors: Yen Mao Hsiung
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/80375758350945112400

碩士 === 國防醫學院 === 藥理學研究所 === 86 === Septic shock is an important clinical issue. The mortality is over 50 %. The main syndromes are tachycardia and hypotension. The treatment for septic shock includes applied of antibiotics, vasoconstrictors, steroids and maintain the volume of circulating system by intravenous supplement of liquid, but these treatments are not efficient. Recently, some scientists pointed out that the conc entration of plasma calcitonin gene-related peptide (CGRP) markedly increased both in septic shock patients and in vivo animal studies. It has been shown that CGRP could induce hypotensive and tachycardiac effects, which are similar to the syndromes of septic shock. Therefore, this study was undertaken to investigate the role of CGRP in septic shock. In the control group, septic shock was induced by intravenous administration of lipopolysaccharde (LPS; 5 mg/kg) in Wistar-Kyoto rats. In the capsaicin group, conscious rats were pretreated with capsaicin (300 mg/kg) subcutaneously for five days to deplete CGRP from sensory nerve endings. Subsequently septic shock was induced by LPS (5 mg/kg, iv).Results demonstrated that the LPS-induced hypotension and tachycardia were improved by the pretreatment of capsaicin. The survival time was significantly prolonged in the capsaicin group when compared with that of control group. The plasma concentrations of TNF-alpha and CGRP were significantly lower in the capsaicin group than those in the control group, whereas the level of plasma nit rate was not significantly different between the two groups. The LPS-induced hypotension can be improved by intravenous infusion of CGRP8-37 ( 30 (mol/min/kg; a specific CGRP antagonist). Furthermore, in isolated aortic rings, the vascular responses to norepinephrine and acetylcholine were reduced after 4 hr of LPS treatment. Pretreatment with capsaicin did not improve this vascular hypo reactivity in LPS-administraed rats. The L-arginine (L-Arg)-induced vasodilati on was also not altered by pretreatment of capsaicin. As forementioned, we summarize that: 1) the plasma concentration of CGRP in LPS-treated rats can be reduced by pretreatment of capsaicin; 2) the syndromes of septic shock can be improved by pretreatment with capsaicin or intravenous infusion of CGRP8-37 ; 3) the LPS-induced increase in plasma nitrate was not affected by pretreatment of capsaicin. In conclusion, the hypotension and tachycardia induced by LPS may be partially caused by the release of CGRP, and the effect of CGRP was not mediated via the activation of the L-Arg-NO pathway. Both of the NO and CGRP pathways and/or NO release CGRP may contribute to the pathogenesis of septic shock.