Epoxyeicosatrienoic Acid Analog and 20-HETE Antagonist Combination Prevent Hypertension Development in Spontaneously Hypertensive Rats.
Epoxyeicosatrienoic Acid Analog and 20-HETE Antagonist Combination Prevent Hypertension Development in Spontaneously Hypertensive Rats.
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DOI：
10.3389/fphar.2021.798642
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发表时间：
2021
影响因子：
5.6
通讯作者：
Kompanowska-Jezierska E
中科院分区：
文献类型：
--
作者：
Baranowska I;Gawrys O;Walkowska A;Olszynski KH;Červenka L;Falck JR;Adebesin AM;Imig JD;Kompanowska-Jezierska E
大量研究表明，细胞色素P-450依赖的花生四烯酸代谢产物在血压调节、血管紧张性和肾功能控制中具有重要作用。环氧二十碳三烯酸(EETs)表现出一系列有益的作用，如血管扩张活性、抗炎、抗纤维化和抗细胞凋亡特性。20-羟基二十碳四烯酸(20-HETE)是一种有效的血管收缩药，可抑制钠在肾脏中的重吸收。本研究观察了EET-A(14，15-EET的稳定类似物)与新型20-HETE受体拮抗剂AAA合用对自发性高血压大鼠(SHR)的降压作用。成年SHR(16周龄)给予两种剂量的EET-A(10或40 mg/kg/d)。在接下来的实验中，我们还测试了选定的物质在预防年轻SHR(6周龄)高血压发展方面的作用。幼鼠给予EET-A或EET-A与AAA合用(均为10 mg/kg/d)。这些物质在饮用水中给药4周。用遥测法测量血压。在代谢笼中进行每周一次的观察；收集尿液、血液和组织样本进行进一步分析。AAA+EET-A的联合治疗在年轻的SHR中显示出降压效果，与对照组相比，观察结束前血压保持在正常水平(收缩压分别为134±2和156±5毫米汞柱；p<；0.05)。此外，联合治疗还增加了一氧化氮代谢产物的排泄。考虑到EET-A和AAA联合治疗对幼年大鼠的有益影响和我们先前在成年SHR中的阳性结果，我们认为它不仅是治疗高血压的一种有前途的治疗策略，而且对于预防高血压也是一种有前途的治疗策略。
Numerous studies indicate a significant role for cytochrome P-450-dependent arachidonic acid metabolites in blood pressure regulation, vascular tone, and control of renal function. Epoxyeicosatrienoic acids (EETs) exhibit a spectrum of beneficial effects, such as vasodilatory activity and anti-inflammatory, anti-fibrotic, and anti-apoptotic properties. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that inhibits sodium reabsorption in the kidney. In the present study, the efficiency of EET-A (a stable analog of 14,15-EET) alone and combined with AAA, a novel receptor antagonist of 20-HETE, was tested in spontaneously hypertensive rats (SHR). Adult SHR (16 weeks old) were treated with two doses of EET-A (10 or 40 mg/kg/day). In the following experiments, we also tested selected substances in the prevention of hypertension development in young SHR (6 weeks old). Young rats were treated with EET-A or the combination of EET-A and AAA (both at 10 mg/kg/day). The substances were administered in drinking water for 4 weeks. Blood pressure was measured by telemetry. Once-a-week observation in metabolic cages was performed; urine, blood, and tissue samples were collected for further analysis. The combined treatment with AAA + EET-A exhibited antihypertensive efficiency in young SHR, which remained normotensive until the end of the observation in comparison to a control group (systolic blood pressure, 134 ± 2 versus 156 ± 5 mmHg, respectively; p < 0.05). Moreover the combined treatment also increased the nitric oxide metabolite excretion. Considering the beneficial impact of the combined treatment with EET-A and AAA in young rats and our previous positive results in adult SHR, we suggest that it is a promising therapeutic strategy not only for the treatment but also for the prevention of hypertension.
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DOI：
10.1152/ajpheart.00831.2001
发表时间：
2003-01-01
影响因子：
4.8
作者：
Falck, JR;Krishna, UM;Campbell, WB
通讯作者：
Campbell, WB
影响因子：
13.6
作者：
Gangadhariah, Mahesha H.;Luther, James M.;Pozzi, Ambra
通讯作者：
Pozzi, Ambra
影响因子：
8.3
作者：
AlonsoGalicia, M;Drummond, HA;Roman, RJ
通讯作者：
Roman, RJ
影响因子：
4
作者：
Alanova, Petra;Huskova, Zuzana;Cervenka, Ludek
通讯作者：
Cervenka, Ludek
影响因子：
56.9
作者：
AKSELROD, S;GORDON, D;COHEN, RJ
通讯作者：
COHEN, RJ