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The combination of atenolol and amlodipine is better than their monotherapy for preventing end-organ damage in different types of hypertension in rats.

Han P, Shen FM, Xie HH, Chen YY, Miao CY, Mehta JL, Sassard J, Su DF - J. Cell. Mol. Med. (2009)

Bottom Line: Baroreflex sensitivity also improved with the combination therapy more than with monotherapy.In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage.The superior effect of the combination was observed in all four models of hypertension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.

ABSTRACT
Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ss-blocker atenolol to modulate end-organ damage. Spontaneously hypertensive rats, DOCA-salt hypertensive rats, two-kidney, one-clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end-organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end-organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage. The superior effect of the combination was observed in all four models of hypertension.

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Effects of long-term treatment with combination of amlodipine and atenolol on blood pressure variability (BPV), heart period variability (HPV) and Baroreflex sensitivity (BRS) in SHR, DOCA, 2K1C and LH. n= 10, mean ± S.D. See Figure 1 for abbreviations. *P < 0.05, **P < 0.01, ***P < 0.001 versus control.
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fig02: Effects of long-term treatment with combination of amlodipine and atenolol on blood pressure variability (BPV), heart period variability (HPV) and Baroreflex sensitivity (BRS) in SHR, DOCA, 2K1C and LH. n= 10, mean ± S.D. See Figure 1 for abbreviations. *P < 0.05, **P < 0.01, ***P < 0.001 versus control.

Mentions: As shown in Figure 2, monotherapy had little effect on systolic blood pressure variability. Atenolol significantly (P < 0.05) decreased systolic blood pressure variability in 2K1C rats and diastolic blood pressure variability in SHR; amlodipine significantly (P< 0.05) decreased systolic blood pressure variability and dias-tolic blood pressure variability in LH. Both systolic blood pressure variability and diastolic blood pressure variability decreased significantly in all four types of hypertension models, with full dose combination therapy. The reduction in systolic blood pressure variability was 33% in SHR (P < 0.001), 43% in DOCA (P< 0.001), 25% in 2K1C (P< 0.01) and 32% in LH (P< 0.01). Half-dose combination therapy (0.5 + 5 mg/kg/d) also significantly reduced systolic blood pressure variability in SHR, DOCA and LH rats and diastolic blood pressure variability in SHR. No significant changes in heart period variability was observed in any group of animals (Fig. 2), with the exception of LH rats treated with full dose of combination in which the heart period variability was significantly decreased (P< 0.05). In this study, baroreflex sensitivity fell in all animals groups, particularly in SHR (0.204 ms/mmHg) and 2K1C (0.281 ms/mmHg) groups of rats in the conscious state.


The combination of atenolol and amlodipine is better than their monotherapy for preventing end-organ damage in different types of hypertension in rats.

Han P, Shen FM, Xie HH, Chen YY, Miao CY, Mehta JL, Sassard J, Su DF - J. Cell. Mol. Med. (2009)

Effects of long-term treatment with combination of amlodipine and atenolol on blood pressure variability (BPV), heart period variability (HPV) and Baroreflex sensitivity (BRS) in SHR, DOCA, 2K1C and LH. n= 10, mean ± S.D. See Figure 1 for abbreviations. *P < 0.05, **P < 0.01, ***P < 0.001 versus control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822879&req=5

fig02: Effects of long-term treatment with combination of amlodipine and atenolol on blood pressure variability (BPV), heart period variability (HPV) and Baroreflex sensitivity (BRS) in SHR, DOCA, 2K1C and LH. n= 10, mean ± S.D. See Figure 1 for abbreviations. *P < 0.05, **P < 0.01, ***P < 0.001 versus control.
Mentions: As shown in Figure 2, monotherapy had little effect on systolic blood pressure variability. Atenolol significantly (P < 0.05) decreased systolic blood pressure variability in 2K1C rats and diastolic blood pressure variability in SHR; amlodipine significantly (P< 0.05) decreased systolic blood pressure variability and dias-tolic blood pressure variability in LH. Both systolic blood pressure variability and diastolic blood pressure variability decreased significantly in all four types of hypertension models, with full dose combination therapy. The reduction in systolic blood pressure variability was 33% in SHR (P < 0.001), 43% in DOCA (P< 0.001), 25% in 2K1C (P< 0.01) and 32% in LH (P< 0.01). Half-dose combination therapy (0.5 + 5 mg/kg/d) also significantly reduced systolic blood pressure variability in SHR, DOCA and LH rats and diastolic blood pressure variability in SHR. No significant changes in heart period variability was observed in any group of animals (Fig. 2), with the exception of LH rats treated with full dose of combination in which the heart period variability was significantly decreased (P< 0.05). In this study, baroreflex sensitivity fell in all animals groups, particularly in SHR (0.204 ms/mmHg) and 2K1C (0.281 ms/mmHg) groups of rats in the conscious state.

Bottom Line: Baroreflex sensitivity also improved with the combination therapy more than with monotherapy.In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage.The superior effect of the combination was observed in all four models of hypertension.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Second Military Medical University, Shanghai, China.

ABSTRACT
Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end-organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ss-blocker atenolol to modulate end-organ damage. Spontaneously hypertensive rats, DOCA-salt hypertensive rats, two-kidney, one-clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end-organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end-organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end-organ damage. The superior effect of the combination was observed in all four models of hypertension.

Show MeSH
Related in: MedlinePlus