ObjectiveTo investigate the influence of norepinephrine on pulmonary vessel pressure in animal model of septic shock. MethodsTwelve health mongrel dogs were randomly divided into a control group (n=5, intravenously injected with normal saline 1 mL/kg) and an endotoxin group(n=7, intravenously injected with lipopolysaccharide 1 mg/kg). When the systemic blood pressure decreased by more than 40% of baseline before administration, the dogs in two groups were intravenously injected with NE 0.5, 1.0, 2.0, 5.0μg·kg-1·min-1. The interval of each dose was more than 10 minutes. The changes of the pulmonary arterial pressure (PAP), pulmonary venous pressure (PVP), and systemic arterial rressure (SAP) were recorded and compared between two groups. ResultsIn the control group, PAP didn't change significantly after administration (P < 0.05), however, PVP increased obviously after NE administration in dose of 2.0 and 5.0μg·kg-1·min-1 (P < 0.05), and SAP increased obviously after NE administration in dose of 1.0, 2.0 and 5.0μg·kg-1·min-1 (P < 0.01). In the endotoxin group, PAP increased obviously after NE administration in dose of 2.0 and 5.0μg·kg-1·min-1 (P < 0.05), while PVP didn't change significantly (P > 0.05), and SAP increased obviously after NE administration in dose of 1.0, 2.0 and 5.0μg·kg-1·min-1 (P < 0.05). There were significant differences in SAP (P < 0.05), not in PAP and PVP (P > 0.05), between two groups after NE administration at dose of 1.0, 2.0 and 5.0μg·kg-1·min-1. The PVP/SAP and PAP/SAP values didn't change significantly after administration in the control group (P > 0.05). In the endotoxin group, the PVP/SAP and PAP/SAP values increased significantly after LPS administration, and decreased slightly after NE administration in dose of 2.0 and 5.0μg·kg-1·min-1 (P < 0.05). ConclusionsNE administration in septic shock can not increase the angiotasis of the pulmonary vein. NE administration in dose of 2.0 and 5.0μg·kg-1·min-1 can cause the increase of PAP and SAP, but the increase of PAP is lower than the increase of SAP.
ObjectiveTo investigate the regulatory roles and changes of M3 receptor subtype in lipopolysaccharide (LPS)-preincubated rabbit pulmonary arteries, and assess the mechanism of altered vascular reactivity in septic shock. MethodsPulmonary arteries with intact endothelium were isolated from 26 male New ealand white rabbits weighing 2.0 to 2.5kg. he isolated pulmonary arteries were randomized into two grouops, including a normal group with normal saline and darifenacin adminstration, and an endotoxin group with LPS-preincubation and darifenacin adminstration.he response of arteries to phenylephrine (100μmol/L) and acetylcholine(ACH)(1μmol/L, 10μmol/L, 100μmol/L)were measured in normal and darifenacin-preincubated circumstances. ResultsThe percentages of ralaxation to ACH (1μmol/L, 10μmol/L, 100μmol/L) were (0.095±0.034)%, (0.150±0.036)%, and (0.445±0.090)% in the normal group, and (0.044±0.016)%, (0.093±0.029)%, (0.311±0.028)% in the endotoxin (LPS 4μg/mL, 4h) group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the EC50 values responding to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 1.483, 2.757, 2.958 in the normal group, and 6.015, 6.242, 6.411 in the endotoxin group. After pretreatment with M3 receptor antagonist darifenacin on different concentrations, the inherent activity of a value to ACH (1μmol/L, 10μmol/L, 100μmol/L) were 0.0146, 0.0323, 0.0825 in the normal group, and 0.0124, 0.0245, 0.0556 in the endotoxin group. ConclusionsLPS pre-incubation can reduce the relaxation response to ACH, and M3 receptor subtypes mediated this relaxation response. LPS also reduce the M3 receptor subtype intrinsic activity, which may be one of the mechanisms of decreased relaxation response to ACH in pulmonary arteris after LPS pretreatment, and also one of the mechanisms of pulmonary hypertension in septic shock.