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Antihypertensive and cardioprotective effects of different monotherapies and combination therapies in young spontaneously hypertensive rats – A pilot study
Saudi Journal of Biological Sciences Pub Date : 2021-09-08 , DOI: 10.1016/j.sjbs.2021.08.093
Christina Hawlitschek 1 , Julia Brendel 1 , Philipp Gabriel 1 , Katrin Schierle 2 , Aida Salameh 3 , Heinz-Gerd Zimmer 1 , Beate Rassler 1
Affiliation  

Spontaneously hypertensive rats (SHR) are an established animal model for antihypertensive treatment. The aim of this pilot study was a systematic search for two lines of antihypertensive treatment – a monotherapy and a combination of two drugs – to be applied in a future study on old SHR. Originally, representatives of three drug classes recommended for antihypertensive therapy in humans should be applied, namely captopril (CAP) as an antagonist of the renin-angiotensin-aldosterone system, nifedipine (NIF) as calcium channel blocker and propranolol (PROP) as β-adrenergic blocker. As we observed that PROP had been poorly ingested, all groups with PROP therapy were excluded from the study. CAP (60 mg kg−1 d-1), NIF (10 mg kg−1 d-1) or both were administered orally to seven-week-old SHR over 3 weeks. A further group of SHR received no treatment (SHR/CTRL). Age-matched normotensive Wistar-Kyoto rats served as normotensive controls. We examined the effect of the antihypertensive therapies on systolic blood pressure, heart weight and on histological and biochemical markers of cardiac hypertrophy and fibrosis.

CAP proved to be the most effective treatment reducing blood pressure and relative heart weight significantly compared to SHR/CTRL without reaching normotensive values. Beginning cardiac fibrosis observed in SHR/CTRL was completely abrogated with CAP treatment. Similar effects were achieved with a combination of CAP and NIF. CAP as monotherapy and CAP + NIF as combination therapy were chosen for the forthcoming study on old SHR.



中文翻译:

不同单一疗法和联合疗法对年轻自发性高血压大鼠的抗高血压和心脏保护作用——一项初步研究

自发性高血压大鼠(SHR)是一种既定的抗高血压治疗动物模型。这项试点研究的目的是系统地寻找两种抗高血压治疗方法——一种单一疗法和两种药物的组合——以应用于未来对旧 SHR 的研究。最初,应使用推荐用于人类抗高血压治疗的三种药物类别的代表,即卡托普利(CAP)作为肾素-血管紧张素-醛固酮系统的拮抗剂,硝苯地平(NIF)作为钙通道阻滞剂和普萘洛尔(PROP)作为β-肾上腺素能阻滞剂。由于我们观察到 PROP 摄入不足,因此所有接受 PROP 治疗的组都被排除在研究之外。CAP(60 mg kg -1 d -1),NIF(10 mg kg -1 d -1) 或两者都在 3 周内对 7 周大的 SHR 进行口服给药。另一组 SHR 未接受任何治疗 (SHR/CTRL)。年龄匹配的正常血压 Wistar-Kyoto 大鼠作为血压正常对照。我们检查了抗高血压治疗对收缩压、心脏重量以及心脏肥大和纤维化的组织学和生化标志物的影响。

与 SHR/CTRL 相比,CAP 被证明是最有效的降低血压和相对心脏重量但没有达到正常血压值的治疗方法。CAP 治疗完全消除了在 SHR/CTRL 中观察到的开始心脏纤维化。CAP 和 NIF 的组合也取得了类似的效果。即将进行的老年 SHR 研究选择了 CAP 作为单一疗法和 CAP + NIF 作为联合疗法。

更新日期:2021-09-08
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