Jovanovic Dijana, Jovovic Djurdjica, Mihailovic-Stanojevic Nevena, Miloradovic Zoran, Naumovic Radomir, Dimitrijevic Jovan, Maksic Nebojsa, Djukanovic Ljubica
Clinic of Nephrology, Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia.
Biomed Pharmacother. 2009 Sep;63(8):571-6. doi: 10.1016/j.biopha.2008.10.006. Epub 2008 Oct 31.
Recent studies indicated pulse pressure as a risk factor for left ventricular hypertrophy, myocardial infarction, congestive heart failure and stroke as well as chronic renal failure progression. The present study examined the effects of carvedilol and its combination with captopril on blood pressure, left ventricular hypertrophy, kidney vascular changes and kidney function in spontaneously hypertensive rats with adriamycin nephropathy. Four groups of 20 SHR each were involved: (1) control group: SHR; (2) ADR group: SHR treated with ADR (2mg/kg i.v. twice in 20 days); (3) ADR-C group: SHR treated with ADR and carvedilol (30 mg/kg/day) and (4) ADR-CC group: SHR treated with ADR and carvedilol (30 mg/kg/day) and captopril (60 mg/kg/day). Systolic-, diastolic- and mean-pressures and pulse pressure were determined at weeks 6 and 12 after the second ADR injection; and body weight, creatinine clearance and proteinuria at weeks -3, 6 and 12. The rats were sacrificed at week 6 or 12, the weights of the left and right ventricles and kidneys measured and the kidney vascular index was calculated as described by Bader and Mayer. Both carvedilol alone and combined with captopril significantly reduced systemic blood pressure but the effect of the latter was more pronounced and registered from week 4 till the end of the study. Carvedilol and its combination with captopril significantly decreased SBP, DBP and MAP. They also decreased PP, prevented the development of LVH, and renal vascular changes and slowed the progression of chronic renal failure and these effects were stronger in the ADR-CC group than in the ADR-C group. The antihypertensive drugs failed to prevent proteinuria in ADR SHR. Significant positive correlations were found between PP (but not SBP, DBP and MAP) and both proteinuria and Ccr in all groups of rats. In conclusion, carvedilol alone, but more strongly in combination with captopril, significantly reduced blood pressure, PP, LVH, renal blood vessel changes and chronic renal failure progression.
近期研究表明，脉压是左心室肥厚、心肌梗死、充血性心力衰竭、中风以及慢性肾衰竭进展的危险因素。本研究考察了卡维地洛及其与卡托普利联用对阿霉素肾病自发性高血压大鼠血压、左心室肥厚、肾血管变化及肾功能的影响。将四组每组20只自发性高血压大鼠纳入研究：（1）对照组：自发性高血压大鼠；（2）阿霉素组：用阿霉素（2mg/kg静脉注射，20天内注射两次）处理的自发性高血压大鼠；（3）阿霉素 - 卡维地洛组：用阿霉素和卡维地洛（30mg/kg/天）处理的自发性高血压大鼠；（4）阿霉素 - 卡维地洛 - 卡托普利组：用阿霉素、卡维地洛（30mg/kg/天）和卡托普利（60mg/kg/天）处理的自发性高血压大鼠。在第二次注射阿霉素后第6周和第12周测定收缩压、舒张压、平均压和脉压；在第 -3周、第6周和第12周测定体重、肌酐清除率和蛋白尿。在第6周或第12周处死大鼠，测量左、右心室及肾脏重量，并按照Bader和Mayer所述方法计算肾血管指数。单独使用卡维地洛及其与卡托普利联用均能显著降低全身血压，但后者的效果更显著，且从第4周直至研究结束均有记录。卡维地洛及其与卡托普利联用均能显著降低收缩压、舒张压和平均动脉压。它们还能降低脉压，预防左心室肥厚的发生以及肾血管变化，并减缓慢性肾衰竭的进展，且这些作用在阿霉素 - 卡维地洛 - 卡托普利组比在阿霉素 - 卡维地洛组更强。抗高血压药物未能预防阿霉素处理的自发性高血压大鼠出现蛋白尿。在所有大鼠组中，脉压（而非收缩压、舒张压和平均动脉压）与蛋白尿和肌酐清除率之间均存在显著正相关。总之，单独使用卡维地洛，但与卡托普利联用效果更强，能显著降低血压、脉压、左心室肥厚、肾血管变化及慢性肾衰竭进展。
