Yang Lufang, Gao Yu-Jing, Lee Robert M K W
Smooth Muscle Research Programme and Department of Anaesthesia, (HSC-2U3), McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Eur J Pharmacol. 2005 Aug 22;518(2-3):145-51. doi: 10.1016/j.ejphar.2005.05.009.
We studied the combined treatment effects of quinapril and atorvastatin on blood pressure and structure and function of resistance arteries from adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY rats). Apoptotic cells were identified by in situ end labeling using the terminal deoxynucleotide transferase-mediated dUTP nick end labeling method. Vascular structure was measured using a morphometric protocol and confocal microscopy and a pressurized artery system was used to study vascular functions. We found that a combined treatment with quinapril and atorvastatin lowered systolic blood pressure in both adult SHR and WKY rats and decreased medial thickness and volume and the number of smooth muscle cell layers in mesenteric arteries, as well as media-to-lumen ratio in the interlobular arteries from SHR but not in those from WKY rats. The number of apoptotic smooth muscle cells was higher in the mesenteric arteries from control WKY rats than control SHR and treatment increased the number of apoptotic smooth muscle cells in the arteries from both SHR and WKY rats. Treatment with quinapril and atorvastatin reduced ventricular weight in SHR and normalized the augmented contractile responses to norepinephrine but did not alter the contraction to electric field stimulation. Relaxation responses to acetylcholine and sodium nitroprusside were not affected by the treatment. We conclude that a combined treatment with quinapril and atorvastatin lowered blood pressure and improved cardiac and vessel hypertrophy and vessel function. An increase in apoptotic smooth muscle cells may be one of the mechanisms underlying the structural improvement.
我们研究了喹那普利和阿托伐他汀联合治疗对成年自发性高血压大鼠(SHR)和正常血压Wistar-Kyoto大鼠(WKY大鼠)血压以及阻力动脉结构和功能的影响。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法,通过原位末端标记鉴定凋亡细胞。使用形态计量学方案和共聚焦显微镜测量血管结构,并使用加压动脉系统研究血管功能。我们发现,喹那普利和阿托伐他汀联合治疗可降低成年SHR和WKY大鼠的收缩压,并减少肠系膜动脉的中膜厚度、体积和平滑肌细胞层数,以及SHR小叶间动脉的中膜与管腔比值,但对WKY大鼠的小叶间动脉无此影响。对照WKY大鼠肠系膜动脉中凋亡平滑肌细胞的数量高于对照SHR,联合治疗增加了SHR和WKY大鼠动脉中凋亡平滑肌细胞的数量。喹那普利和阿托伐他汀治疗可降低SHR的心室重量,并使对去甲肾上腺素增强的收缩反应恢复正常,但不改变对电场刺激的收缩。对乙酰胆碱和硝普钠的舒张反应不受治疗影响。我们得出结论,喹那普利和阿托伐他汀联合治疗可降低血压,改善心脏和血管肥大以及血管功能。凋亡平滑肌细胞增加可能是结构改善的潜在机制之一。