核受体和α-肾上腺素能激动剂亚型在自发性高血压大鼠新陈代谢和全身血液动力学中的相互作用

IF 3.5 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
PPAR Research Pub Date : 2024-06-07 eCollection Date: 2024-01-01 DOI:10.1155/2024/5868010
Sheryar Afzal, Munavvar Abdul Sattar, Ibrahim Albokhadaim, Ali Attiq, Mahmoud Kandeel, Aimi Syamima Abdul Manap, Sameer M Alhojaily
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引用次数: 0

摘要

部分和完全 PPAR-γ 激动剂通过增加血浆脂肪直通素的浓度,显示出了抗高血压和抗糖尿病药物的良好效果。本研究的目的是研究在SHRs中单独使用部分和完全PPAR-γ受体激动剂亚组治疗后,以及在与促肾上腺皮质激素联用时,PPAR-γ、α-肾上腺素受体和促肾上腺皮质激素受体在调节血管紧张素II(Ang II)和肾上腺素受体激动剂的血管舒张反应中的作用。还测定了这些动物的抗氧化潜能和代谢指数。第一组(WKY)和第二组(SHR)分别为正常血压对照组和高血压对照组。第三组(SHR)和第四组(SHR)口服厄贝沙坦(30 毫克/千克)和吡格列酮(10 毫克/千克)28 天,第五组(SHR)、第六组(SHR)和第七组(SHR)仅在第 21 至 28 天分别腹腔注射单用、与厄贝沙坦联用和与吡格列酮联用的脂肪生成素(2.5 微克/千克)。第29天,用戊巴比妥钠(60毫克/千克)麻醉所有受试动物,并测定全身血液动力学和血浆脂肪连通素浓度以及体内外抗氧化潜能。与 WKY 对照组相比,SHR 对照组的无创血压和基础平均动脉压明显升高,动脉僵硬度增加,血浆一氧化氮、脂肪连接蛋白浓度和抗氧化酶水平降低(均 P < 0.05)。然而,单药治疗可使所有组的上述症状逐渐恢复正常,SHR + Irb + Adp 组的恢复程度更高(P < 0.05)。在急性研究中,与 WKY 相比,SHR 对静脉注射肾上腺素能激动剂和血管紧张素-II 的剂量依赖性平均动脉压反应明显要大 20-25%。在 SHR + Pio + Adp 组中,单独使用或联合使用脂肪连接蛋白可明显减弱对这些α-肾上腺素能激动剂的血管加压反应,减弱幅度为 63%,而在 SHR + Irb + Adp 组中,对 ANG-II 给药的反应减弱幅度为 70%。总之,脂肪素与 PPAR 激动剂联合治疗可降低全身血管对肾上腺素能激动剂的反应,并改善动脉僵化。这证明在 SHRs 的全身血管中,脂肪素受体、PPAR-γ、α-肾上腺素受体和 ANG-II 相互作用。PPAR-γ 完全激动剂和脂肪粘连素受体之间的协同作用也得到了证实。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interaction between Nuclear Receptor and Alpha-Adrenergic Agonist Subtypes in Metabolism and Systemic Hemodynamics of Spontaneously Hypertensive Rats.

Partial and full PPAR-γ agonists have shown promising effects and antihypertensive and antidiabetic agents through increased plasma adiponectin concentration. This study is aimed at examining the role of PPAR-γ, alpha-adrenoceptors, and adiponectin receptors in the modulation of vasopressor responses to angiotensin II (Ang II) and adrenergic agonists, after a subset treatment of partial and full PPAR-γ agonists, each individually, and also when coupled with adiponectin in SHRs. The antioxidant potential and metabolic indices for these animals were also determined. Group I (WKY) and group II (SHR) were designated as normotensive control and hypertensive control, respectively. Groups III (SHR) and IV (SHR) received irbesartan (30 mg/kg) and pioglitazone (10 mg/kg) orally for 28 days, and groups V (SHR), VI (SHR), and VII (SHR) were treated with adiponectin (2.5 μg/kg) intraperitoneally alone, in combination with irbesartan, and in combination with pioglitazone, respectively, from days 21 to 28 only. On day 29, sodium pentobarbitone (60 mg/kg) was used to anesthetize all test animals, and systemic hemodynamic and plasma adiponectin concentrations and in vitro and in vivo antioxidant potential were measured. As compared to the WKY control, the SHR control group's noninvasive blood pressure and basal mean arterial pressure were significantly greater, along with increased arterial stiffness, lower plasma nitric oxide, adiponectin concentration, and antioxidant enzyme levels (all P < 0.05). However, they were gradually normalized by single drug treatments in all groups, and to a greater extent in the SHR + Irb + Adp group (P < 0.05). In the acute study, the dose dependant mean arterial pressure responses to intravenously administered adrenergic agonists and angiotensin-II were significantly larger in SHRs as compared to WKY by 20-25%. Adiponectin alone and in combination significantly blunted vasopressor responses to these alpha-adrenergic agonists in the SHR + Pio + Adp group by 63%, whereas attenuated responses to ANG-II administration to 70% in SHR + Irb + Adp. In conclusion, the combined treatment of adiponectin with PPAR-agonists reduced the systemic vascular responses to adrenergic agonists and improved arterial stiffness. This an evidence of the interaction of adiponectin receptors, PPAR-γ, alpha-adrenoceptors, and ANG-II in the systemic vasculature of SHRs. A significant level of synergism has also been proved among full PPAR-γ agonists and adiponectin receptors.

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来源期刊
PPAR Research
PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.20
自引率
3.40%
发文量
17
审稿时长
12 months
期刊介绍: PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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