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一氧化氮-环磷酸鸟苷-钾通道通路参与含马蒂厄斯(Martius)油纳米胶囊的降压作用。

NO-cGMP-K Channels Pathways Participate in the Antihypertensive Effects of Martius ex Spreng Oil-Loaded Nanocapsules.

作者信息

de Azevedo Maria Medina, Lívero Francislaine Aparecida Dos Reis, Tinelli Sílvia Beatriz Bürger, da Silva Jacenir Vieira, de Almeida Danielle Ayr Tavares, Martines Marco Antonio Utrera, Prada Ariadna Lafourcade, Rodríguez Amado Jesús Rafael, Gasparotto Junior Arquimedes

机构信息

Laboratory of Cardiovascular Pharmacology (LaFaC), Faculty of Health Sciences, Federal University of Grande Dourados (UFGD), Dourados 79804-970, MS, Brazil.

Laboratory of Cardiometabolic Pharmacology, Department of Pharmacology, Federal University of Parana (UFPR), Curitiba 80060-000, PR, Brazil.

出版信息

Pharmaceutics. 2024 Jun 21;16(7):842. doi: 10.3390/pharmaceutics16070842.

Abstract

Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease.

摘要

源自施普伦格的马蒂乌斯棕榈是一种广泛分布于巴西中西部地区的棕榈树。在本研究中,我们调查了载油纳米胶囊(APON)对雄性自发性高血压大鼠(SHR)是否具有急性和持久的降压作用,并探讨了其潜在的分子机制。APON采用界面聚合物沉积法制备。使用动态和电泳光散射研究了粒径、多分散指数和zeta电位。在急性十二指肠给药后和口服治疗7天后,评估了APON(剂量为1、3和10mg/kg)的降压作用。为了研究其中涉及的分子途径,我们使用了针对前列腺素/环磷酸腺苷、一氧化氮/环磷酸鸟苷和钾通道的药理学拮抗剂和抑制剂。急性和长期给予APON(剂量为3和10mg/kg)均导致收缩压、舒张压和平均动脉压显著降低。预先用非选择性一氧化氮合酶抑制剂(Nω-硝基-L-精氨酸甲酯)、鸟苷酸环化酶抑制剂(亚甲蓝)或非选择性钙敏感性钾通道阻滞剂(四乙铵)治疗可消除APON的降压作用。我们的研究表明,载油纳米胶囊在短期和长期(7天)使用后对SHR均具有显著的降压作用。这种作用似乎依赖于血管内皮功能,并且涉及NO-cGMP-K通道途径。这项研究为未来明确证明APON在治疗心血管疾病中的治疗益处的研究指明了新方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f617/11279957/adb00f217546/pharmaceutics-16-00842-g001.jpg

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