目的:探究有氧运动对高血压大鼠(SHR)肠系膜动脉血管平滑肌细胞大电导钙激活钾(BKCa)通道α和β1亚基蛋白表达及血管舒缩性的影响.方法:选用12周龄雄性自发性高血压大鼠(SHR,n=24)以及正常血压对照组(WKY,n=12).将SHR随机分组,高血压安静对照组(SHR,n=12)和高血压有氧运动组(SHR-EX,n=12),各组大鼠先进行1周适应性训练,之后SHR-EX组进行为期8周的跑台训练.9周后,取各组大鼠的肠系膜动脉(2~3级),进行HE染色,离体微血管张力测定及蛋白免疫印迹分析.结果:(1)SHR组肠系膜动脉的管壁厚度明显高于WKY组(P<0.01),但SHR-EX组肠系膜动脉的管壁厚度明显低于SHR组(P<0.01);(2)Iberiotoxin(10-7M)作为BKCa通道选择性阻断剂可诱发各组血管张力增加,增高幅度为SHR>SHR-EX>WKY,NS11021作为BKCa通道选择性激动剂可使血管张力下降,下降幅度为SHR>SHE-EX>WKY;(3)SHR组BKCa通道的α和β1亚基表达上调,且以β1亚基上调更为显著,SHR-EX组的两亚基上调减弱,且以β1亚基变化更为显著.结论:高血压诱导大鼠肠系膜动脉BKCa通道功能增强,负反馈调节血管张力增加,但有氧运动可显著抑制高血压伴随的大鼠肠系膜动脉BKCa通道的α和β1亚基表达上调,从而改善血管功能.
Objective: The present study was designed to investigate the effects of chronic exercise on the molecular expression of α- and [31-subunit of large-conductance Ca2+-activated K+ (BKCa) channels and vascular contractility in rat mesenteric arterial smooth muscle cells from spontaneously hyperten- sive rats. Methods: Three-month-old male normotensive Wistar-Kyoto rats (WKY, n=12) and SHRs (n=24) were used. SHRs (n=24) were separated into a sedentary group (SHR) and an exercise group (SHR-EX) at random (n=12 in each group). After a 1-week acclimation period, rats in SHR-EX were sub- jected to aerobic excrelse on a motor-driven treadmill. After 8 weeks, HE staining was used to analyze the vascular morphology change. Mesenteric arterial tensions were measured in vitro. Immunohistochemistry and Western blots assay were also conducted. Results: 1 ) Compared with WKY, the systolic blood pressure and pulse pressure were significantly increased with hypertension (P〈0.01 ). However, they significantly dropped in SHR-EX compared with its sed- entary group (P〈O.01). 2) The wall thickness of mesenteric artery in hypertension group was obviously increased, but it effectively decreased in SHR-EX compared with SHR. Selective BKCa channel blocker (Iberiotoxin10-7M) induced a marked increase of vascular tension in MAs in all three groups. Howev- er, these effects were greatly increased in SHR group. 3) Selective BKCa channel activator (NS11021) induced concentration-dependent vasorelaxation in MAs precontracted with norepinephrine. However, these effects were greatly decreased in SHR group. 4) Western blotting showed that the protein expression of BKCa ct- and β-subunit was significantly increased with hypertension, and the increase of β1 subunits was larger than that of α subunits, whereas aero- bic exercise could effectively ameliorate the changes. Conclusions : Hypertension is associated with an increase of BKCa channel protein expression, which is a negativ