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.
Objective To compare the vasoactive effects of norepinephrine( NE) and dopamine of different doses on isolated rabbit pulmonary and systemic arteries in septic shock. Methods Six paired pulmonary and systemic arterial rings were prepared fromsix rabbits, and matched randomly assigned into a normal group and a LPS group. The assigned groups were intervened by different doses of NE. Another six paired pulmonary and systemic arterial rings were prepared from another six rabbits. They were assigned to different groups as above and intervened by different doses of dopamine. The LPS groups were pre-incubated in RPMI mediumsupplemented with4 μg/mL LPS to simulate septic shock. The tension of arterial rings was measured and its response to NE and dopamine were studied. Results ( 1) In the normal groups, the contraction of the systemic arteries was ber than the pulmonary arteries in response to low,middle dose of NE, and high dose of dopamine ( all P lt; 0. 05) , and which was weaker in response to middle dose of dopamine and similar in response to high dose of NE( P gt;0. 05) . Both the pulmonary and systemic arteriesrelaxed in response to low dose of dopamine. ( 2) After LPS pre-incubation, the contraction of the systemic arteries was weaker than the pulmonary arteries in response to low dose of dopamine ( P lt;0. 05) , and which was similar in response to low,middle and high dose of NE, and middle, high dose of dopamine. ( 3) Comparing the LPS groups with the normal groups, the contraction in response to middle dose of dopamine increased in the systemic arteries and dreased in the pulmonary arteries ( P lt;0. 05) . Conclusions In septic shock, the vasoactive effect of different doses of NE is not different between pulmonary and systemic arteries. But middle dose of dopamine can increase the contraction of systemic arteries and decrease the contraction of pulmonary arteries.