| Clinically, monotherapy is effective only in 50% patients in achieving optimal blood pressure (BP) control. Therefore treatment with two or more antihypertensive drugs belonging to different classes is often necessary. Combination antihypertensive drugs simplify dosing regimens, improve compliance, improve hypertension control, decrease dose-dependent side-effects, and reduce cost as the first-line treatment of hypertension. High BP level is not the unique factor determining hypertensive end-organ damage. It has been proposed that blood pressure variability (BPV) may be an important factor determining end organ damage in hypertension. In addition, arterial baroreflex dysfunction (BRS) is another feature of hypertension. It has been well recognized that BRS is impaired in hypertensive humans and animals. In an attempt to create an operational index of the duration of antihypertensive activity, T/P ratio was introduced in 1988 for clinical evaluation of a drug with long-lasting action. It was believed that the measurement of T/P ratio in SHR would provide meaningful information for the evaluation of antihypertensive agents like ACE inhibitors.This work was designed to investigate the possible synergism of atenolol and amlodipine on lowering blood pressure and to study the importance of reduction of blood pressure variability (BPV) in the organ protection of long-term treatment with combination of amlodipine and atenolol in spontaneously hypertensive rats (SHR).At first, sixty-four SHR were randomly divided into 8 groups. They wererespectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10 mg/kg), amlodipine (0.5, 1, 2 mg/kg) and the combinations of atenolol and amlodipine (10 + 0.5, 10 + 1, and 10 + 2 mg/kg). The drugs were given via a catheter of gastric fistula. Blood pressure was recorded from one hour before drug administration for 25 hours in conscious freely moving rats. It was found that combination of atenolol and amlodipine significantly decreased blood pressure and systolic blood pressure variability. From probability sum analysis, it was found that the combination of atenolol and amlodipine with a proportion of 10:1 was the best combination (q=1.54). Trough: peak ratio of the combination of atenolol and amlodipine (10:1) was the highest (79%). In conclusion, the present work clearly demonstrated that the combination of atenolol and amlodipine is synergistic in lowering and stabilizing BP. The synergism is greatest when the dose proportion of the 2 drugs is 10:1.To study the effect of the organ protection of long-term treatment with combination of amlodipine and atenolol in SHR. Sixty SHR were randomly divided into 6 groups. Normal diet without drugs (control), atenolol (10 mg/kg), amlodipine (1 mg/kg) and the combinations of atenolol and amlodipine (5 + 0.5, 10 + 1, and 20 + 2 mg/kg/d) were given in rat chow for 16 weeks in SHR. Blood pressure (BP) was then recorded during 24 hours in conscious state. After the determination of baroreflex sensitivity, rats were killed for organ-damage evaluation. Long-term treatment with three combinations of atenolol and amlodipine significantly decreased BP and BPV, ameliorated impaired BRS. Three combinations could obviously preventleft ventricular hypertrophy and aortic hypertrophy. And the combination of atenolol and amlodipine (10+1, 20+2 mg/kg/d) could distinctly prevent renal atrophy. The indexes of left ventricular and aortic hypertrophy, and renal atrophy were all positively related to BP and BPV, and negatively related to BRS in untreated and SHR treated. Stepwise multiple-regression analysis shows that decrease in left ventricular was mainly related to the decrease in systolic BP; decrease in aortic hypertrophy was mainly related to decrease in systolic BPV and increase in BRS; and amelioration in renal lesion was mainly determined by increase in BRS and decrease in systolic BPV. From this study, we found that long-term treatment with the combinations of atenolol and amlodipine possessed obvious organ protection in SHR. Besides t...
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