乙醇对血管11β羟化固醇脱氢酶Ⅱ型及血压的影响

Effects of alcohol on blood pressure and vascular 11β-hydroxysteroid dehydroge nase type Ⅱ

目的 :验证乙醇对血管 11β羟化固醇脱氢酶Ⅱ型及血压的影响并探讨其机制。方法 :检测饮酒者 80例及非饮酒者 (对照组 ) 2 0例的血压及血浆皮质醇水平 ;雄性Wistar大鼠 4 0只随机分为 4组 :对照组 (10只 ) ,其它 3组 (各10只 )分别给予外源性乙醇 0 .7、1.4和 2 .1g·kg-1·d-1(分别为乙醇 1组、乙醇 2组和乙醇 3组 )共 3个月。观察血压及血浆皮质醇水平变化、肠系膜动脉对去甲肾上腺素的加压反应、肠系膜血管网离体灌注液中皮质醇及醛固酮的含量 ,以及通过RT PCR观察主动脉 11β羟化固醇脱氢酶Ⅱ型及醛固酮合成酶mRNA表达的变化。 结果 :饮酒组血压升高 ,收缩压 139± 1、舒张压 94± 8,对照组收缩压 12 2± 9、舒张压 81± 5mmHg,两组比较P <0 .0 1,饮酒组血浆皮质醇 14 9.6± 2 5 .7ng/L ,显著高于对照组 12 3.8± 2 3.0ng/L(P <0 .0 1)。给予乙醇使Wistar大鼠动脉血压升高(P <0 .0 1) ,血浆皮质醇水平升高 ,乙醇 1组 15 1.0± 4 8.2 ,2组 2 14 .8± 91.0 ,3组 35 7.1± 113.3;对照组 86 .1± 36 .1ng/L(P <0 .0 1)。肠系膜动脉对去甲肾上腺素的加压反应增强 (P <0 .0 1。肠系膜血管网离体灌注液中皮质醇含量增高 ,乙醇 1组 113.8± 14 .6 ,2组 12 2 .3± 15 .9,3组 131.5± 18.8;对照组 70 .7± 6 .

AIM:To search for the role of alcohol on blood pressure and va sc ular 11β-hydroxysteroid dehydrogenase type Ⅱ.METHODS: Levels of blood pressure and cortisol were measured in 80 male subjects with alcohol co nsumption.Forty Male Wister rats were divided into four groups:①control group( n=10),②alcohol-treated (0.7 g· -1kg·d -1) group 1(n=10), ③alcohol-treated (1.4 g· -1kg·d -1) group 2(n=10), ④alcohol -treated (2.1 g· -1kg·d -1) group 3(n=10). The blood pressure was measured after 1 months, 2 months and 3 months.The serum corticosterone was measured after 3 months. Mesenteric artery perfusion ex vivo and pressor re sponses to norepinephrine was performed. The perfusate from the mesenteric arter ies was collected and applied to a reverse phase high performance liquid chromat ography,and measured for both aldosterone and corticosterone by radioimmunoassay .RT-PCR was used to measure the expression of 11β HSD2 and aldosterone syntha se(CYP11B2)mRNA. RESULTS: Levels of blood pressure and cortisol we re significantly increased in subjects with alcohol consumption compared to cont rol subjects(P<0.01). Systolic blood pressure increased in Wister rats tre ated with alcohol compared to control rats(P<0.01).The pressor responses to norepinephrine in mesenteric arteries treated with alcohol was signficantly incr eased(P<0.01). Levels of aldosterone were decreased but those of corticoste rone increased in the perfusate from arteries treated with alcohol(P<0.01).R T-PCR showed that cholic acid inhibited the expression of 11β HSD2 and CYP11B2 mRNA in arteries.CONCLUSION: These results reveal that alcohol is able to induce hypertension and provide evidence that alcohol inhibit the trans cription of both 11β HSD2 and CYP11B2 in vasculature,leading to lower aldoster one and higher corticosterone production in vessels and increased vasoconstricto r responses to norepinephrine.