卡维地洛改善自发性高血压大鼠左室舒张功能及机制探讨

The effect and mechanism of carvedilol on left ventricular myocardium relaxation in spontaneously hypertensive rats

目的探讨卡维地洛对自发性高血压大鼠(SHR)心肌细胞肌质网(SR)膜上钙泵活性的影响及机制。方法将12周龄雄性SHR40只随机分成4组,每组10只。第1组在未作治疗时即测定各项指标,并与同周龄Wistar大鼠(10只)比较,作为治疗前对照。另3组经0.85%氯化钠、倍他洛克、卡维地洛治疗20周后,观察各项指标的变化。结果与Wistar大鼠比较,SHR的平均动脉压、左室肥厚指数、左室舒张末压明显增高,心肌细胞SR膜上钙泵活性明显降低(P<0.05)。经治疗后,倍他洛克与卡维地洛有相同的降血压及减慢心率作用,但卡维地洛降低左室舒张末压、左室肥厚指数及提高心肌细胞SR膜上钙泵活性作用比倍他洛克强(P<0.05)。结论卡维地洛能显著提高心肌细胞SR膜上钙泵活性,降低左室舒张末压,其与全面阻滞α1、β1、β2后逆转左室肥厚,减低外周血管阻力后减少心肌耗氧量有关。

Objective:To investigate the effect of carvedilol on calcium pump in membrane of sarcoplasmic reticulum (SR) and its regulative mechanism in spontaneously hypertensive rats (SHR) and possible mechanism. Methods:Forty SHRs of 12 weeks old were divided into 4 groups ( n =10): control(c), NS, betalocbet and carvedilolcar. Heart rate(HR), mean blood pressure(MBP), left ventricular mass index(LVMI), left ventricular end-diastolic pressure(LVEDP) and calcium pump of membrane of SR were determined. Wistar rats ( n =10)of matched age were also served as control of before treatment. Results:Compared with wistar rats, MBP, LVMI and LVEDP were increased and activity of calcium pump was decreased clearly in SHRc( P < 0.05 ). After 20 weeks treatment compared with SHRc, HR of SHRBet are as slower as that of SHRCar and MBP of SHRbet and SHRcar was slower and MBP of SHRbet and SHRcar was lower. However compared with SHRbet, LVMI and LVEDP of SHRcar were decreased more significantly ( P < 0.05 ); the calcium pump activity were greatly increased ( P < 0.05 ). Conclusions: Our results showed that carvidilol via blocking α_1β_1 and β_2 receptor reversed left ventricular hypertrophy, decline peripheral vascular resisted and decreased cardiac oxygen consumption so as to enhance calcium pump activity and reduce LVEDP.