钾通道抑制剂减弱吉非罗齐对离体大鼠胸主动脉环的舒张作用

Potassium channel blockers attenuate vasorelaxation induced by gemfibrozil in rat isolated thoracic aortic ring

目的观察吉非罗齐对大鼠离体胸主动脉肌源性反应的影响,并探讨其作用机制。方法采用离体血管张力方法观察吉非罗齐对SD大鼠胸主动脉环静息张力及苯肾上腺素(PE)预收缩的影响;观察一氧化氮合成酶(NOS)抑制剂、环氧合酶抑制剂和K+通道阻断剂对吉非罗齐作用的影响。结果吉非罗齐(1×10-5～3×10-4mol.L-1)对大鼠胸主动脉静息张力无影响,但对PE(10-6mol.L-1)所致的预收缩具有浓度依赖性舒张作用,其最大舒张率为最大舒张的80.42%±6.35%。电压依赖性钾通道(KV)阻断剂四氨基吡啶(4-AP,10-3mol.L-1)、钙激活钾通道(KCa)阻断剂四乙胺(TEA,10-2mol.L-1)、内向整流钾通道(KIR)阻断剂氯化钡(BaCl2,10-3mol.L-1)和ATP敏感钾通道(KATP)阻断剂格列苯脲(Gli,10-5mol.L-1)均可减弱吉非罗齐的血管舒张作用(P<0.05),而一氧化氮合酶(NOS)抑制剂L-NAME(10-4mol.L-1)及环氧酶抑制剂吲哚美辛(10-5mol.L-1)对吉非罗齐的舒张作用无影响(P>0.05)。结论吉非罗齐对大鼠主动脉具有舒张作用,该舒张作用与NO及前列环素无关;可能与开放KV、KCa、KIR和KATP通道有关。

Aim To investigate the myogenic effects of gemfibrozil on rat isolated vascular smooth muscle and to explore the underlying mechanism. Methods Ten- sion of isolated thoracic aortic rings of male Sprague Dawley （SD） rats was recorded by PowerLab. The effect of gemfibrozil on the quiescent thoracic aortic rings and rings precontracted by phenylephrine （PE） were studied. L-NAME, an inhibitor of oxide synthase （ NOS ）, indomethacin, an inhibitor of cyclooxygen- ase, and K ＋ channel blockers were used to explore the vasorelaxing mechanism of gemfibrozil. Result Gem- fibrozil （1 × 10-5 -3× 10-4mol·L-1） had no effect on quiescent aortic rings （ P 〉 0.05 ）. Gemfibrozil re- laxed the precontractions induced by PE （10-6mol·L-1） in a concentration-dependent manner. The vaso- dilator effect of gemfibrozi] was significantly attenuated by BaC12（1 mmol L-l）, TEA （10 mmol L-1）, 4- AP （1 mmol. L-1） and Gli （0.01 mmol L-1） （p 〈 0. 05）. Neither L-NAME （0. 1 mmol L-1 ） nor in- domethacin （0. 01 mmol L-1） affected the vasodila- tor effect of gemfibrozi] （ P 〉 0. 05 ）. Conclusions Gemfibrozil relaxes KtR, Kv, Kca and oids synthesis may vasodilatation. contracted rat aorta. Activation of KATP, but neither NO nor prostan- be involved in gemfibrozil-induced vasoclilatation.