Abstract
Aim:
To test the effects of atenolol and amlodipine, either alone or in combination, on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS), and the prevalence of stroke in stroke-prone spontaneously hypertensive rats (SHR-SP).
Methods:
In the first set of the study, 24 8-month-old, female SHR-SP rats were randomly divided into 3 groups. Blood pressure, heart period, and BRS were determined before and after the intragastric administration of atenolol (10 mg/kg) and amlodipine (1.0 mg/kg), either alone or in combination. In the second set of the study, 40 male and 40 female rats were randomly assigned to 1 of the following 4 groups: control, atenolol (10 mg·kg−1·d−1), amlodipine (1.0 mg·kg−1·d−1), and both (10 male and 10 female in each group). The stroke incident and survival time were recorded.
Results:
Atenolol and amlodipine, either alone or in combination, significantly decreased blood pressure, with the exception of the amlodipine-induced effect on diastolic blood pressure. Meanwhile, only the combination treatment significantly decreased the BPV levels for the same period. The q-values calculated by the probability sum analysis were 1.17 and 2.67 for systolic and diastolic blood pressure, respectively, and were 2.48 and 2.10 for systolic and diastolic BPV, respectively, following administration. Neither drug exhibited any significant effect on BRS. Atenolol and amlodipine, either alone or in combination, significantly increased the lifespan of SHR-SP, with the best effect elicited by the combination therapy.
Conclusion:
A significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure in SHR-SP. Combination therapy may be an optimal strategy for the prevention of stroke in hypertension.
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References
He J, Gu D, Wu X, Reynolds K, Duan X, Yao C, et al. Major causes of death among men and women in China. N Eng J Med 2005; 353: 1124–34.
Mackay J, Mensah G . The atlas of heart disease and stroke. Geneva, Switzerland: World Health Organization; 2004.
Luepker RV, Arnett DK, Jacobs DR Jr, Duval SJ, Folsom AR, Armstrong C, et al. Trends in blood pressure, hypertension control, and stroke mortality: the Minnesota Heart Survey. Am J Med 2006; 119: 42–9.
Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense HW, Joffres M, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA 2003; 289: 2363–9.
Reducing the burden of stroke. Lancet 2005; 366: 1752.
Materson BJ, Reda DJ, Cushman WC, Massie BM, Freis ED, Kochar MS, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med 1993; 328: 914–21.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo, JL, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72.
Shen FM, Xie HH, Ling G, Xu LP, Su DF . Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats. Acta Pharmacol Sin 2005; 26: 1303–8.
Xu LP, Shen FM, Shu H, Miao CY, Jiang YY, Su DF . Synergism of atenolol and amlodipine on lowering and stabilizing blood pressure in spontaneously hypertensive rats. Fundam Clin Pharmacol 2004; 18: 33–8.
Xie HH, Miao CY, Jiang YY, Su DF . Synergism of atenolol and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats. J Hypertens 2005; 23: 193–201.
Yamori Y, Horie R, Handa H, Sato M, Fukase M . Pathogenic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans. Stroke 1976; 7: 46–55.
Wang J, Shen FM, Wang MW, Su DF Effects of nine antihypertensive drugs on blood pressure variability in sinoaortic-denervated rats. Acta Pharmacol Sin 2006; 27: 1013–7.
Shen FM, Zhang SH, Xie HH, Jing Q, Wang DS, Su DF . Early structural changes of aortic wall in sinoaortic-denervated rats. Clin Exp Pharmacol Physiol 2006; 33: 358–63.
Gu XW, Xie HH, Wang J, Shen FM, Su DF . Arterial baroreflex is not involved in salt preference in rats. Clin Exp Pharmacol Physiol 2006; 33: 607–11.
Miao CY, Xie HH, Zhan LS, Su DF . Blood pressure variability is more important than blood pressure level in determination of end-organ damage in rats. J Hypertens 2006; 24: 1125–35.
Jin ZJ . About the evaluation of drug combination. Acta Pharmacol Sin 2004; 25: 146–7.
Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR . The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med 1990; 150: 1881–4.
Weir MR . The rationale for combination versus single-entity therapy in hypertension. Am J Hypertens 1998; 11: S163–9.
Waeber B, Detry JM, Dahlof B, Puig JG, Gundersen T, Hosie J, et al. Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy? Am J Hypertens 1999; 12: 915–20.
Menard J . Critical assessment of combination therapy development. Blood Press 1993; 1 Suppl: 5–9.
Parati G, Pomidossi G, Albini F, Malaspina D, Mancia G . Relationship of 24-hour blood pressure mean and variability to severity of target-organ damage in hypertension. J Hypertens 1987; 5: 93–8.
Su DF, Miao CY . Blood pressure variability and organ damage. Clin Exp Pharmacol Physiol 2001; 28: 709–15.
Su DF, Miao CY . Reduction of blood pressure variability: a new strategy for the treatment of hypertension. Trends Pharmacol Sci 2005; 26: 388–90.
Liu AJ, Ma XJ, Shen FM, Liu JG, Chen H, Su DF . Arterial baroreflex: a novel target for preventing stoke in rat hypertension. Stroke 2007; 38: 1916–23.
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Project supported by the National Hi-Technology Research and Development Programme (863 project, No 2006AA02Z4C1) and the Science and Technology Development Foundation of Shanghai (No 04JC14001).
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Ling, G., Liu, Aj., Shen, Fm. et al. Effects of combination therapy with atenolol and amlodipine on blood pressure control and stroke prevention in stroke-prone spontaneously hypertensive rats. Acta Pharmacol Sin 28, 1755–1760 (2007). https://doi.org/10.1111/j.1745-7254.2007.00630.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00630.x
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