Objectivesa) To determine the response of endotoxin-exposed vascular smooth muscle to exogenous vasoconstrictors during concomitant exposure to an inhaled anesthetic (halothane); and b) to determine if excess nitric oxide production is responsible for any altered response.DesignIn vitro, prospective, repeated-measures, dose-response study.SettingUniversity/medical school experimental physiology laboratory.SubjectsAdult male Sprague-Dawley rats, whose aortae were studied in an in vitro preparation.InterventionsThoracic aortae were excised from anesthetized animals and cut into 3-mm rings. After incubation in aerated organ baths containing a modified essential medium with or without Escherichia coli lipopolysaccharide (100 micro gram/mL) at 37 degrees C for 5 hrs, the rings were removed and suspended in separate baths for isometric tension recording. Phenylephrine dose-response data (10minus10 to 10minus5 M) were determined for lipopolysaccharide- and nonlipopolysaccharide-treated rings. After washout and equilibration, two vessels (one each lipopolysaccharide- and nonlipopolysaccharide-treated) were additionally exposed to 2% halothane and phenylephrine dose-response determinations were repeated for all vessels. This procedure was repeated for 1% halothane in a separate experiment. In some experiments, the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine (3 times 10minus4 M), was added to the bath after the washout from the second phenylephrine dose-response determination. Then, a third phenylephrine dose-response determination was performed, with and without 2% halothane.Measurements and Main ResultsDose-response curves were evaluated using a logistic regression analysis. In addition, absolute and percentage changes in tension were compared between the first and second contractions. Exposure to lipopolysaccharide resulted in a decrease in the maximum tension from 2.07 plus minus 0.03 (controls) to 1.24 plus minus 0.04 g/mg of vessel dry weight and an increase in the dose at which the contraction is 50% of maximum (ED50) from 3.78 times 10minus8 to 2.05 times 10minus7 M (p less than .05). Exposure to 2% halothane produced significant reductions in the maximum tensions in both groups. The lipopolysaccharide-treated vessels showed not only a proportionately larger decrease (minus 51 plus minus 5% vs. minus 18 plus minus 2% in the control plus halothane group), but also a significantly greater absolute decrease (0.59 plus minus 0.09 vs. 0.34 plus minus 0.04 g/mg in the control plus halothane group). The addition of 1% halothane produced less pronounced decreases in tension, with only an additive effect in the lipopolysaccharide-treated vessels. The addition of Nomega-nitro-L-arginine resulted in a reversal of the lipopolysaccharide-induced decrease in tension. However, 2% halothane still had a significantly greater effect on the lipopolysaccharide-exposed rings.ConclusionsExposure of rat aortic rings to lipopolysaccharide in vitro decreased the contractile response to phenylephrine. The addition of 2% halothane resulted in a more than additive decrease in tension in the lipopolysaccharide-treated vessels. Patients in septic or endotoxic shock are sensitive to most anesthetic regimens, and some of this sensitivity may be due to an altered vasoconstrictive response induced by lipopolysaccharide exposure. The inability of nitric oxide synthase inhibition to reverse this response completely suggests that induction of nitric oxide synthase and increased production of nitric oxide are not solely responsible for this finding.(Crit Care Med 1996; 24:287-293)