肾动脉平滑肌细胞BKCa变化对自发性高血压大鼠肾血管重构及肾小球滤过率的影响

Age-related change and its significance of BKCa in renal artery smooth muscle cells of spontaneously hypertensive rats

目的探讨大电导钙激活钾通道(BKCa,MaxiK)随大鼠增龄的变化及其与血压水平、肾血管重构及肾小球滤过率(GFR)的关系。方法选取雄性15、21、27周龄自发性高血压大鼠(SHR)及正常大鼠(对照组),每组各6只,测定各组大鼠腹主动脉血压,24h尿肌酐、血肌酐,计算内生肌酐清除率(Ccr)代表GFR。利用膜片钳全细胞模式记录肾动脉血管平滑肌细胞(VSMCs)钾电流、膜电容(Cm),计算BKCa电流值和电流密度。对肾动脉作常规病理切片和HE染色,进行形态学观察及血管内径(LD)、血管中膜厚度(MT)、中膜与内径比(MT/LD)的测量与计算。结果不同周龄SHR腹主动脉平均动脉压(MABP)均明显高于正常大鼠(P<0.05)。SHR肾动脉VSMCs Cm随周龄增加而增大,电流密度则逐渐降低,正常大鼠无此变化。SHR肾动脉LD减小及MT、MT/LD增大各周龄间有统计学意义(P均<0.05),正常大鼠则无明显变化。SHR GFR随增龄减小显著(P<0.05),正常大鼠无明显变化。SHR肾动脉VSMCs BKCa电流密度与Cm,腹主动脉MABP,肾动脉血管LD、MT、MT/LD,GFR均高度相关(r分别为-0.7962、-0.7361、0.8275、-0.7923、-0.6492、0.7612)。而正常大鼠肾动脉VSMCs BKCa电流密度与腹主动脉MABP相关(r=-0.4761)。结论BKCa电流和电流密度随周龄增加而衰减,血压水平是衰减程度的重要反应。BKCa电流密度随增龄衰减与高血压肾血管重构及GFR高度相关。

Objective To observe the change of large-conductance calcium-activated potassium channels（ BK- Ca, MaxiK） along with age and its relationships with blood pressure, renal vascular remodeling and glomerular filtration rate（GFR） in rats. Methods Eighteen male spontaneously hypertensive rats （SHR） aged 15, 21, 27 weeks as hypertension group, and eighteen corresponding aged normal rats as control group were selected. Abdominal aortic blood pressure of rats were measured. The urine creatinine and serum creatinine value in 24 hours were tested, and calculated creatinine clearance rate（Ccr）, which was on behalf of GFR. The potassium current, capacitance of membrane（Cm） of vascular smooth muscle cells（VSMCs） of renal artery were recorded, and the BKCa current, the potassium current density and the BKCa current density were calculated. The renal arteries were stained to observe the changes of blood vessel morphous along with age, including vessel lumen diameter（LD）, media thickness（MT） and MT/LD. Results The mean abdominal aortic blood pressure （MABP） of SHR in different aged groups was obviously higher than that of normal rats（P 〈 0. 05 ）. The Cm of renal arterial VSMCs increased with age in SHR group, but it wasn＇t in normal group. The BKCa current density of SHR renal arterial VSMCs decreased with age, but the change of normal rats with age had no significant difference. The LD of SHR renal arteries decreased with age and MT, MT/LD of renal arteries in SHR increased with age（P 〈0. 05）, but it wasn＇t found in normal group. Compared with normal group, the GFR of SHR group significantly decreased. The BKCa current density was correlated with Cm, MABP, LD, MT, MT/ LD and GFR in SHR（r was -0. 7962, -0. 7361, 0. 8275, -0. 7923, -0. 6492, -0. 7612 respectively）, but it was correlated with MABP only in normal group（ r = - 0. 4761 ）. Conclusion BKCa current and current density have a age-related decline in SHR, and the decline was highly correlated with the vascular remodeling of hypertension and GFR.