NO/cGMP signal pathway involved in the disturbance of calcium homeostasis in vascular smooth muscle during the late phase of sepsis / 浙江大学学报·医学版

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the alterations in calcium metabolism of the vascular smooth muscle of rat thoracic aorta in the late phase of sepsis and to investigate the involvement of nitric oxide (NO)/cyclic-GMP(cGMP) signal transduction pathway in the sepsis-induced vascular hyporeactivity.</p><p><b>METHODS</b>Male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Eighteen hours post CLP, rat aortic rings were removed for measurement of contractile responses to vasoconstrictors by using organ bath technique.</p><p><b>RESULT</b>In endothelium intact aortic rings from CLP rats, concentration-contraction curves to phenylephrine (PE) and high KCl were significantly decreased when compared with those from control rats. The transient contraction induced by PE in calcium-free Krebs solution and the concentration-dependent contraction to CaCl(2)in KCl-depolarized medium were also markedly reduced. The hyporeactivity to vasoconstrictors was completely reversed by pretreatment either with aminoguanidine (AMG), a selective inducible nitric oxide synthase inhibitor, or with 1H [1,2,4] oxadiazolo[4,3-a] quininoxalin-1-one(ODQ), an inhibitor of NO-sensitive guanylyl cyclase.</p><p><b>CONCLUSION</b>A generalized impairment in calcium handling in vascular smooth muscle,including the calcium influx through the voltage-operated and receptor-operated channels and calcium release from intracellular calcium stores, is involved in vascular hyporeactivity during the late phase of sepsis. The NO/cGMP signal transduction pathway might be involved in this defect in vascular smooth muscle.</p>