| Objective: Abnormal vascular reactivity is one of the most important pathophysiological changes in endotoximia. The predominant hemodynamic features are systemic hypotension and pulmonary artery hypertension in early phase.lt has been proved that lipopolysaccharides(LPS),the major active component of endotoxin, causes oxiadant injury to vascular tissues, moreover ,LPS induces extraordinary expressions and productions of endothelium-dependent relaxing factors nitric oxide(NO), carbon monoxide(CO) and their related enzymes, which aggravates the abnormal vascular reactivity. Recently, melatonin(MT), a hormone secreted by pineal, was found to have potent antioxidant activity. Studies have confirmed that MT can protest injury caused by many oxidants, but there is no report about the effect of MT on the changes of vascular reactivity during endotoximia. The purpose of present study was to investigate the effect of MT on the vascular reactivity of systemic and pulmonary circulation induced by endotoxin, and the mechanisms were also preliminarily studied.Methods: The effect of MT on changes of thoracic aorta and pulmonary artery was observed separately.Spaugue-Dwley rats were divided into four groups randomly(1)Vehicle group: 0.9% saline,i.p.;(2)LPS group: LPS 4mg/kg ,i.p.; (3)LPS+MT group: LPS 4mg/kg i.p.,before LPS injection 30min and after LPS injection 60min MT 5mg/kg ,i.p.;(4)MT group: 5mg/kg, i.p.,and after the first injection 90min give another same dose of MT.Six hours after LPS or saline injection or five hours after the second injection in MT group, rats were killed and the thoracic aortic rings (TARs) and pulmonary artery rings (PARs) were removed. The reactivity of artery rings in the four subgroups of TARs and PARs was tested separately. The contraction response to phenylephrine (PE) and the endo- thelium-dependent relaxation response (EDRR) to acetylcholine (ACh) were tested. Concentration-response curves were generated with ACh or PE (lO'Mo^mol/L). In order to assess the involve- ment of NO and CO, inducible NO synthase inhibitor aminoguani- dine (AG), non-selective NO synthase (NOS) inhibitor N'"-nitro-L- arginine (L-NNA) or heme oxygenase-l(HO-l) inhibitor zinc protopor-phyrin factor-alpha (ZnPP) was added separately to the chambers and allowed to remain in contact with TARs or PARS for 20 mins ,then rings were tested with lO^mol/L PE and ACh again. SOD activity ,contents of MDA and NO were detected.The structure of pulmonary artery and thoracic aorta was observed under light microscope(LM) and scanning electron microscope (SEM).The data were divided into two parts according to TARs and PARs. Statistical analysis was carried in the two parts separately .All the data were presented as mean D. Differences among each four subgroups were tested by one-way analysis of variance (ANOVA)followed by a Newman-Keuls q test when significant differences were detected ,paired student'/ test was employed before and after agents administration in each subgroup. P valus of less than 0.05 were considered statistically significant.Results: For TARs ,LPS significantly reduced the contraction response to PE compared with vehicle group(P<0.01) and the curve of cumulative dose responses to PE(10"8-10~5mol/L)in LPS group shifted right .Although EDRR to ACh in LPS group had the tendency to decrease but still had no significant difference compared with vehicle group(PX).05) . For PARs, EDRR to ACh was depressed significantly in LPS group (PO.01), while no effect on contraction response to PE in LPS group was observed compared with vehicle group(P> 0.05).Compared with LPS group, TARs in LPS+MT group exhibited increased contraction response to PE ,but still lower than vehicle group. Similarly JEDRR to ACh by PARs in LPS+MT group was improved significantly and there was no difference between LPS+MT group and vehicle group .The vascular reactivity was unaffected in MT group compared with vehicle group both in TARs and in PARs.Preincubation with AG or ZnPP for 20 mins,the contractile response to PE incre... |
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