Kähönen M, Karjala K, Hutri-Kähönen N, Wu X, Jaatinen P, Riihioja P, Hervonen A, Pörsti I
Department of Pharmacological Sciences, University of Tampere Medical School, FIN-33101 Tampere, Finland.
Am J Physiol. 1999 Feb;276(2):H464-71. doi: 10.1152/ajpheart.1999.276.2.H464.
The aim of this work was to evaluate the effects of long-term ethanol consumption on arterial responses in vitro in young and aged rats. Therefore, Wistar rats (ages 3 and 29 mo, respectively) were allocated to six groups: control-young, sucrose-young, ethanol-young, control-aged, sucrose-aged, and ethanol-aged. The ethanol-fed groups were given 25% ethanol by intragastric gavage three times a day 4 days a week. Responses of mesenteric arterial rings were examined in standard organ chambers after 5 treatment weeks. In norepinephrine-precontracted arterial rings, endothelium-dependent relaxations to acetylcholine, as well as endothelium-independent relaxations to isoproterenol, were attenuated in aged rats when compared with young controls. Relaxation responses to isoproterenol, but not to acetylcholine and nitroprusside, were clearly improved by ethanol treatment in both young and aged rats. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, enhanced the relaxation to acetylcholine in all three aged rat groups but was without significant effect in the young rats. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester the relaxation to acetylcholine in control and sucrose-fed aged rats was markedly reduced compared with control rats, whereas in the young controls and in both young and aged ethanol-exposed groups, distinct relaxations to higher concentrations of acetylcholine were still present. The endothelium-independent relaxations to cromakalim, a hyperpolarizing vasodilator acting via ATP-sensitive potassium channels, were also markedly augmented by ethanol feeding in both young and aged rats. In conclusion, ethanol consumption in both young and aged rats was associated with markedly improved arterial relaxations to isoproterenol and cromakalim, as well as clearly augmented relaxation to acetylcholine during inhibition of cyclooxygenase and nitric oxide synthase. These findings suggest that especially the potassium channel-related component of arterial relaxation was augmented by long-term ethanol exposure.
本研究的目的是评估长期摄入乙醇对年轻和老年大鼠离体动脉反应的影响。因此，将Wistar大鼠（分别为3月龄和29月龄）分为六组：年轻对照组、年轻蔗糖组、年轻乙醇组、老年对照组、老年蔗糖组和老年乙醇组。给予乙醇喂养组25%乙醇，通过胃内灌胃，每周4天，每天3次。治疗5周后，在标准器官浴槽中检测肠系膜动脉环的反应。与年轻对照组相比，在去甲肾上腺素预收缩的动脉环中，老年大鼠对乙酰胆碱的内皮依赖性舒张以及对异丙肾上腺素的非内皮依赖性舒张均减弱。在年轻和老年大鼠中，乙醇处理均能明显改善对异丙肾上腺素的舒张反应，但对乙酰胆碱和硝普钠的反应无明显改善。环氧化酶抑制剂双氯芬酸可减少舒张和收缩性前列腺素的合成，在所有三个老年大鼠组中均增强了对乙酰胆碱的舒张作用，但对年轻大鼠无显著影响。在一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯存在的情况下，与对照大鼠相比，对照和蔗糖喂养的老年大鼠对乙酰胆碱的舒张作用明显降低，而在年轻对照组以及年轻和老年乙醇暴露组中，对较高浓度乙酰胆碱仍有明显的舒张作用。通过ATP敏感性钾通道起作用的超极化血管舒张剂克罗卡林的非内皮依赖性舒张，在年轻和老年大鼠中也因乙醇喂养而明显增强。总之，年轻和老年大鼠摄入乙醇均与对异丙肾上腺素和克罗卡林的动脉舒张明显改善以及在环氧化酶和一氧化氮合酶抑制期间对乙酰胆碱的舒张明显增强有关。这些发现表明，长期乙醇暴露尤其增强了动脉舒张中与钾通道相关的成分。
