GENETIC BASIS FOR SEX-RELATED HYPER-RESPONSIVENESS TO SEVERE PULMONARY ARTERIAL HYPERTENSION INDUCED BY SU5416 IN A SUB-STRAIN OF SPRAGUE DAWLEY RATS

2015 ◽  
Vol 31 (10) ◽  
pp. S79-S80
Author(s):  
K.R. Chaudhary ◽  
Y. Deng ◽  
A. Yang ◽  
D.J. Stewart
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Genetic Basis ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial ◽  
Severe Pulmonary Arterial Hypertension

Effect of TSN3015 on the development of pulmonary arterial hypertension in male Sprague-Dawley rats

2019 ◽  
Vol 99 ◽  
pp. 106595
Author(s):  
Peter B. Senese ◽  
Kimberly Doherty ◽  
David Bullough ◽  
Vinicius Carreira ◽  
Michael Gralinski
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial

scholarly journals Rosiglitazone Attenuated Endothelin-1-Induced Vasoconstriction of Pulmonary Arteries in the Rat Model of Pulmonary Arterial Hypertension via Differential Regulation of ET-1 Receptors

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yahan Liu ◽  
Xiao Yu Tian ◽  
Yu Huang ◽  
Nanping Wang
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arteries ◽  
Progressive Increase ◽  
Differential Regulation ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular failure and death. Activation of the endothelin (ET)-1 system has been demonstrated in plasma and lung tissue of PAH patients as well as in animal models of PAH. Recently, peroxisome proliferator-activated receptorγ(PPARγ) agonists have been shown to ameliorate PAH. The present study aimed to investigate the mechanism for the antivasoconstrictive effects of rosiglitazone in response to ET-1 in PAH. Sprague-Dawley rats were exposed to chronic hypoxia (10% oxygen) for 3 weeks. Pulmonary arteries from PAH rats showed an enhanced vasoconstriction in response to ET-1. Treatment with PPARγagonist rosiglitazone (20 mg/kg per day) with oral gavage for 3 days attenuated the vasocontractive effect of ET-1. The effect of rosiglitazone was lost in the presence ofL-NAME, indicating a nitric oxide-dependent mechanism. Western blotting revealed that rosiglitazone increasedETBRbut decreasedETARlevel in pulmonary arteries from PAH rats.ETBRantagonist A192621 diminished the effect of rosiglitazone on ET-1-induced contraction. These results demonstrated that rosiglitazone attenuated ET-1-induced pulmonary vasoconstriction in PAH through differential regulation of the subtypes of ET-1 receptors and, thus, provided a new mechanism for the therapeutic use of PPARγagonists in PAH.

scholarly journals Rosuvastatin ameliorates the development of pulmonary arterial hypertension in the transgenic (mRen2)27 rat

2009 ◽  
Vol 297 (3) ◽  
pp. H1128-H1139 ◽  
Author(s):  
Vincent G. DeMarco ◽  
Javad Habibi ◽  
Adam T. Whaley-Connell ◽  
Rebecca I. Schneider ◽  
James R. Sowers ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
No Synthase ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial

We have recently reported that transgenic (mRen2)27 rats (Ren2 rats) exhibit pulmonary arterial hypertension (PAH), which is, in part, mediated by oxidative stress. Since 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exhibit beneficial vascular effects independent of cholesterol synthesis, we hypothesized that rosuvastatin (RSV) treatment ameliorates PAH and pulmonary vascular remodeling in Ren2 rats, in part, by reducing oxidative stress. Six-week-old male Ren2 and Sprague-Dawley rats received RSV (10 mg·kg−1·day−1 ip) or vehicle for 3 wk. After treatment, right ventricular systolic pressure (RVSP) and mean arterial pressure (MAP) were measured. To evaluate treatment effects on pulmonary arteriole remodeling, morphometric analyses were performed to quantitate medial thickening and cell proliferation, whereas whole lung samples were used to quantitate the levels of 3-nitrotyrosine, superoxide, stable nitric oxide (NO) metabolites [nitrates and nitrites (NO x)], and expression of NO synthase isoforms. In the Ren2 rat, RVSP is normal at 5 wk of age, PAH develops between 5 and 7 wk of age, and the elevated pressure is maintained with little variation through 13 wk. At 8 wk of age, left ventricular function and blood gases were normal in the Ren2 rat. Ren2 rats exhibited elevations in medial hypertrophy due to smooth muscle cell proliferation, 3-nitrotyrosine, NO x, NADPH oxidase activity, and endothelial NO synthase expression compared with Sprague-Dawley rats. RSV significantly blunted the increase in RVSP but did not reduce MAP in the Ren2 rat; additionally, RSV significantly attenuated the elevated parameters examined in the Ren2 rat. These data suggest that statins may be a clinically viable adjunct treatment of PAH through reducing peroxynitrite formation.

scholarly journals Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats

2016 ◽  
Vol 310 (11) ◽  
pp. L1088-L1097 ◽  
Author(s):  
C. M. Happé ◽  
M. A. de Raaf ◽  
N. Rol ◽  
I. Schalij ◽  
A. Vonk-Noordegraaf ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Endothelial Cell Proliferation ◽  
Pulmonary Vasculature ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Pulmonary Arterial ◽  
Severe Pulmonary Arterial Hypertension

The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6. Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. This study describes the SuPNx model, which features severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our study, together with previous studies on experimental models of pulmonary hypertension, shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover, and ongoing apoptosis, represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature.

scholarly journals Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension

2021 ◽  
Vol 118 (11) ◽  
pp. e2023899118
Author(s):  
Takeshi Masaki ◽  
Makoto Okazawa ◽  
Ryotaro Asano ◽  
Tadakatsu Inagaki ◽  
Tomohiko Ishibashi ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Aryl Hydrocarbon Receptor ◽  
Vascular Lesions ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Aryl Hydrocarbon ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Here, we explore the role of AHR in the pathogenesis of PAH. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. Sprague–Dawley rats treated with the potent endogenous AHR agonist, 6-formylindolo[3,2-b]carbazole, in combination with hypoxia develop severe pulmonary hypertension (PH) with plexiform-like lesions, whereas Sprague–Dawley rats treated with the potent vascular endothelial growth factor receptor 2 inhibitors did not. Ahr-knockout (Ahr−/−) rats generated using the CRISPR/Cas9 system did not develop PH in the SU5416/hypoxia model. A diet containing Qing-Dai, a Chinese herbal drug, in combination with hypoxia led to development of PH in Ahr+/+ rats, but not in Ahr−/− rats. RNA-seq analysis, chromatin immunoprecipitation (ChIP)-seq analysis, immunohistochemical analysis, and bone marrow transplantation experiments show that activation of several inflammatory signaling pathways was up-regulated in endothelial cells and peripheral blood mononuclear cells, which led to infiltration of CD4+ IL-21+ T cells and MRC1+ macrophages into vascular lesions in an AHR-dependent manner. Taken together, AHR plays crucial roles in the development and progression of PAH, and the AHR-signaling pathway represents a promising therapeutic target for PAH.

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