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目的观察醛固酮对血管外膜诱导型一氧化氮合酶(iNOS)/一氧化氮(NO)通路的影响及作用机制。方法取sD大鼠胸主动脉外膜,分别给予不同浓度醛固酮(ALD)10~(-8)～10~(-6)mol/L、ALD+螺内酯以及 ALD+RU486进行孵育,此外在给予脂多糖激活血管外膜 iNOS/NO 的情况下,观察以上各组药物刺激后 iNOS/NO 系统的变化。与上述药物共同孵育6 h 后通过 Griess 法测定相对稳定的代谢产物硝酸盐和亚硝酸盐(NOx)代表 NO 的产生量,采用[~3H]-L-精氨酸标记的同位素法测定外膜 iNOS 活性。结果 (1)NOx 产生的变化:ALD 刺激后血管外膜 NOx 生成无明显变化。用螺内酯拮抗盐皮质激素受体后,高浓度 ALD 组(10~(-7)～10~(-6)moL/L)血管外膜 NOx 产生呈下降趋势(P<0.05)。用 RU486拮抗糖皮质激素受体后随 ALD 浓度增加 NOx 生成量也呈浓度依赖性增加(P<0.01)。脂多糖刺激后上述趋势更为明显。(2)iNOS 活性的变化:ALD 刺激后 iNOS 活性无明显变化,螺内酯刺激后血管外膜 iNOS 活性有下降趋势,但无统计学意义。而 RU486刺激后血管外膜 iNOS 活性显著增加(P<0.05)。同时给予脂多糖刺激后,螺内酯+ALD 组血管外膜 iNOS 活性显著下降(P<0.01),ALD+RU486组血管外膜 iNOS 活性显著增加(P<0.05)。结论 ALD 主要通过盐皮质激素受体和糖皮质激素受体通路两种途径直接影响血管外膜 iNOS/NO 系统,醛固酮作用于盐皮质激素受体能够诱导 iNOS 激活、刺激 NO 产生,作用于糖皮质激素受体抑制 iNOS/NO 激活。
Objective To observe the effect of aldosterone on iNOS / NO pathway and its mechanism. Methods The adventitia of thoracic aorta of sD rats were treated with different concentrations of aldosterone (ALD) 10 ~ (-8) ~ 10 ~ (-6) mol / L, ALD + spironolactone and ALD + RU486 respectively. Activation of iNOS / NO of vascular adventitia was observed in the above groups of drug-induced changes in iNOS / NO system. After incubation with the above drugs for 6 h, the relative steady metabolites nitrate and nitrite (NO x) were measured by Griess method to represent the production of NO. The [3H] -L-arginine labeled isotope method was used to determine the outer membrane iNOS activity. Results (1) Changes of NOx production: There was no significant change in the formation of extravascular nitric oxide after ALD stimulation. After the spironolactone antagonized the mineralocorticoid receptor, the production of nitric oxide was decreased (P <0.05) in high concentration ALD group (10 ~ (-7) ~ 10 ~ (-6) molL / L) Inhibition of glucocorticoid receptor with RU486 also increased concentration of NOx with concentration of ALD in a concentration-dependent manner (P <0.01). The above trend is more obvious after lipopolysaccharide stimulation. (2) The changes of iNOS activity: There was no significant change of iNOS activity after ALD stimulation, while the activity of iNOS decreased after spironolactone stimulation, but there was no statistical significance. However, the iNOS activity of the adventitia was significantly increased after RU486 stimulation (P <0.05). At the same time, the activity of iNOS in spironolactone + ALD group was significantly decreased (P <0.01). The activity of iNOS in ALD + RU486 group was significantly increased (P <0.05). CONCLUSION: ALD directly affects iNOS / NO system of vascular adventitia mainly through mineralocorticoid receptor and glucocorticoid receptor pathway. Aldosterone acts on mineralocorticoid receptor to induce iNOS activation, stimulates NO production and acts on glucocorticoids Hormone receptors inhibit iNOS / NO activation.