Tetramethylpyrazine Inhibits Hypoxia-Induced Pulmonary Vascular Leakage in Rats via the ROS-HIF-VEGF Pathway.
Summary of "Tetramethylpyrazine Inhibits Hypoxia-Induced Pulmonary Vascular Leakage in Rats via the ROS-HIF-VEGF Pathway."
Tetramethylpyrazine (TMP) is a reactive oxygen species (ROS) antagonist that has potent properties for the treatment of a variety of vascular diseases, such as ischemic stroke and pulmonary hypertension secondary to chronic obstructive pulmonary diseases. However, there are few data about the role of TMP in hypoxia-induced pulmonary vascular leakage. This study examined the effect of TMP on hypoxia-induced pulmonary vascular leakage and the underlying mechanisms. Rat pulmonary microvascular endothelial cells (RPMVECs) treated with TMP or not were subjected to hypoxic or normoxic conditions for 24 h, and the monolayer permeability, intracellular ROS, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins levels were determined. Additionally, rats administrated TMP were exposed to hypobaric hypoxia to evaluate the effect of TMP in vivo by measuring lung water content, pulmonary vascular leakage into the lungs and immunohistochemistry for HIF-1α and VEGF. Hypoxia was found to cause a significant increase in RPMVEC monolayer permeability and intracellular ROS, HIF-1α and VEGF protein levels. Treatment with TMP decreased the hypoxia-induced RPMVEC monolayer permeability and attenuated the elevation of ROS, HIF-1α and VEGF protein levels. TMP-treated animals showed less pulmonary vascular leakage and HIF-1α and VEGF expression compared with those exposed to hypoxia alone. These observations supported that TMP inhibited the increase in pulmonary vascular permeability induced by hypoxia. The underlying mechanisms may be related to the scavenging of intracellular ROS and the suppression of hypoxia-induced upregulation of HIF-1α and VEGF proteins.
Affiliation
Base for Drug Clinical Trials, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Journal Details
This article was published in the following journal.
Name: Pharmacology
ISSN: 1423-0313
Pages: 265-273
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21494058
- DOI: http://dx.doi.org/10.1159/000326082
Medical and Biotech [MESH] Definitions
Epoprostenol
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Pulmonary Veno-occlusive Disease
Pathological process resulting in the fibrous obstruction of the small- and medium-sized PULMONARY VEINS and PULMONARY HYPERTENSION. Veno-occlusion can arise from fibrous proliferation of the VASCULAR INTIMA and VASCULAR MEDIA; THROMBOSIS; or a combination of both.
Pulmonary Heart Disease
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Hypertension, Pulmonary
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.
Rats, Long-evans
An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.
PubMed Articles
Nifedipine inhibits hypoxia induced transvascular leakage through down regulation of NFkB.
We have studied the prophylactic administration of nifedipine and its molecular mechanism involved in reducing the transvascular leakage and inflammation in rats under hypoxia. Rats exposed to an alti...
Cardiac atria are the primary source of ANP release in hypoxia-adapted rats.
AIMS: Atrial natriuretic peptide (ANP) is released from the heart in response to hypoxia and helps mitigate the development of pulmonary hypertension. However, the mechanism of hypoxia-induced ANP rel...
Role of RhoB in the Regulation of Pulmonary Endothelial and Smooth Muscle Cell Responses to Hypoxia.
Rationale: RhoA and Rho kinase contribute to pulmonary vasoconstriction and vascular remodeling in pulmonary hypertension. RhoB, a protein homologous to RhoA and activated by hypoxia, regulates neopla...
Background: Evidence indicates that protein kinase C (PKC) plays a pivotal role in hypoxia-induced pulmonary hypertension (PH), but PKC isoform-specific protein expression in pulmonary arteries and th...
The proliferation of pulmonary artery smooth muscle cells (PASMCs) plays a role in pulmonary vascular remodeling (PVR). Recently, it was shown that vascular smooth muscular cell phenotype modulation i...
Clinical Trials
Effects of Bosentan (Tracleer) in the Course of Pulmonary Artery Hypertension Induced by Hypoxia
Excessive rise in pulmonary artery pressure induced by low oxygen tension (hypoxia) is one of the factors implicated in high-altitude pulmonary oedema. Plasma ET1 increases in subjects ex...
Hypoxia Impairs Endothelial Function in HAPEs
Aim of the study is to investigate the function of the systemic vascular endothelium in individuals susceptible to high-altitude pulmonary oedema during normoxia and normobaric hypoxia.
Biomarkers in the Evaluation of Chronic Lung Disease
We hypothesize that hypoxia-induced pulmonary vascular remodeling is mediated by macrophage migration inhibitory factor (MIF), that remodeling is in fact the reflection of a chronic inflam...
Catecholamines Can Attenuate Intermittent Hypoxia-Induced Expression of TNF in Human Monocytes
Specific aim To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients (2). To map th...
Circulating Endothelial Compartment During Normal and Pathological Aging
This part of the project aims to describe changes in markers of vascular competence (Endothelial Microparticles Platelet (EMP), Circulating endothelial cells (CEC) and Circulating endothel...
