Escherichia coli-induced inhibition of endothelium-dependent relaxation and gene expression and release of nitric oxide is attenuated by chronic alcohol ingestion.

ABSTRACT

We examined the effect of chronic administration of ETOH on Escherichia coli-mediated suppression of relaxation and nitric oxide (NO) production by the rat thoracic aorta (RTA) and gene expression for constitutive NO synthase (cNOS) by the adrenal gland. Chronic alcoholic rats ("alcoholic") were fed a diet containing ETOH as 36% of the caloric intake for 8-10 weeks. Nonalcoholic control rats ("control") were fed an isocaloric equivalent diet containing 36% dextrin. Alcoholic rats were given an injection of approximately approximately 10(10) live E. coli through a dorsal SC catheter 24 and 19 h before experimentation ("alcoholic-septic"), and control rats were treated in an identical manner ("septic"). The next day the rats were anesthetized with ketamine-xylazine (0.1 ml/100 g rat) and rings of RTA were mounted in muscle chambers for isometric recording of force development. Rings of RTA were precontracted with an EC50 concentration of phenylephrine, and relaxation to acetylcholine (ACh), A23187, and nitroglycerin were obtained. A23187- and ACh-induced relaxation was attenuated in RTA obtained from septic rats, whereas the relaxation to nitroglycerin was slightly enhanced. Chronic administration of ETOH attenuated the effects of E. coli on endothelium-dependent relaxation in alcoholic-septic rats. NO was measured with ozone chemiluminescence. Basal and stimulated NO production was attenuated in RTA obtained from septic rats and unaffected in RTA obtained from alcoholic or alcoholic-septic rats. cNOS was unmeasurable in adrenals from septic rats. ETOH increased mRNA for cNOS, an effect amplified in alcoholic-septic rats. Thus, E. coli inhibits endothelium-dependent relaxation and NO production, and ETOH attenuates these effects of E. coli on the endothelium-NO system, possibly by upregulating gene expression for cNOS.