Effects of combination therapy with atenolol and amlodipine on blood pressure control and stroke prevention in stroke-prone spontaneously hypertensive rats

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 ), 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. Key wordsstroke; hypertension; stroke-prone; spont a ne ou sl yhy per t ensi ve r a t s ; a t eno l ol ; amlodipine; blood pressure; blood pressure variability

A Randomized, Comparative, Multicentric Evaluation of Atenolol/Amlodipine Combination with Atenolol Alone in Essential Hypertensive Patients

“…11 Preliminary studies in stroke-prone spontaneously hypertensive rats have shown that significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure. 14 The results of our study confirmed that the combination therapy with atenolol/amlodipine is superior to atenolol monotherapy in patients with mild-to-moderate essential hypertension.…”

Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro

“…The probability sum test was used to determine whether the effect of the combination of the two drugs was synergistic. This test was first proposed by Jin in 1980 31 and subsequently adapted for evaluating the synergism of two antihypertensive drugs 32,33 . In the present work, we found that in cultured neonatal rat cardiomyocytes, cell viability and cardiomyocyte apoptosis was markedly influenced by pretreatment with either losartan or simvastatin, and that these effects were markedly enhanced when the two drugs were used in combination.…”

Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis <I>in vitro</I>

“…This test was first proposed by Jin in 1980 [31] and subsequently adapted for evaluating the synergism of two antihypertensive drugs. [32,33] In the present work, we found that in cultured neonatal rat cardiomyocytes, cell viability and cardiomyocyte apoptosis was markedly influenced by pretreatment with either losartan or simvastatin, and that these effects were markedly enhanced when the two drugs were used in combination. The q values for cell viability and cardiomyocyte apoptosis were 1.31 and 1.21, respectively.…”