Fasudil attenuates sympathetic nervous activity in the adrenal medulla of spontaneously hypertensive rats

Kumai, Toshio; Takeba, Yuko; Matsumoto, Naoki; Nakaya, Shinji; Yoshimitsu, Tetsuo; Yanagida, Yohei; Hayashi, Muneaki; Kobayashi, Shinichi

doi:10.1016/j.lfs.2007.08.008

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…Y27632, the first ROCK inhibitor described, decreases blood pressure in 11-Deoxycorticosterone acetate (DOCA)-salt rat model of hypertension. A similar effect was obtained with the newer ROCK inhibitors fasudil, SAR07899, in other animal models of hypertension, including the spontaneously hypertensive rat (SHR), angiotensin II-induced hypertension in several animals, and L-NG-Nitroarginine Methyl Ester (L-NAME)-induced hypertension ( Uehata et al, 1997 ; Mukai et al, 2001 ; Kumai et al, 2007 ; Lohn et al, 2009 ). Of note, this class of inhibitors also has a major part of their effect on hypertension through inhibition of inflammatory pathways and cardiovascular remodeling.…”

Section: Vascular Smooth Muscle Signal Transductionsupporting

confidence: 57%

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

et al. 2016

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The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function.

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Section: Vascular Smooth Muscle Signal Transductionsupporting

confidence: 57%

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

et al. 2016

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“…In vivo inhibition of Rock by treatment with Y27632 decreases blood pressure in the DOCA-salt rat model of hypertension. 2 This finding has then been confirmed by the use of other Rock inhibitors such as fasudil and SAR407899 in other animal models including spontaneously hypertensive rats (SHR), 23,24 Ang II-induced hypertension, 25 and L-NAME-induced hypertension (Fig. 3).…”

Section: Role Of Rac1 In Vascular Smooth Muscle Contractionmentioning

confidence: 68%

Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension

Loirand

Pacaud

2014

Small GTPases

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“…MCP-1 through the activation of CCR2 can induce migration and attachment of monocytes/macrophages, lymphocytes, endothelial cells and vascular smooth muscle cells [ 50 ]. Tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthetic pathway, is increased in the adrenal medulla of SHR [ 51 ]. Neuropeptide Y (NPY) is a 36-amino acid peptide neurotransmitter, released from postganglionic sympathetic perivascular neurons [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model

Lan

et al. 2021

Chin Med

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Background Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. Methods The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). Results LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. Conclusions LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.

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Fasudil attenuates sympathetic nervous activity in the adrenal medulla of spontaneously hypertensive rats

Cited by 9 publications

References 26 publications

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

Involvement of Rho GTPases and their regulators in the pathogenesis of hypertension

A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model

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