HIGH MORTALITY OF FISCHER VS. SPRAGUE-DAWLEY RATS IN THE SU5416 MODEL OF SEVERE PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH STRAIN-SPECIFIC FAILURE OF RIGHT VENTRICULAR ADAPTATION: EFFECTS OF CARDIAC-SPECIFIC THERAPY WITH CARDIOTROPHIN-1

2015 ◽  
Vol 31 (10) ◽  
pp. S142-S143
Author(s):  
C. Suen ◽  
M. Al-Ghani ◽  
B. Jiang ◽  
Y. Deng ◽  
M. Taha ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
High Mortality ◽  
Sprague Dawley ◽  
Specific Therapy ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial ◽  
Severe Pulmonary Arterial Hypertension ◽  
Adaptation Effects

Abstract 15922: Fischer Rats Exhibit High Mortality in the Su5416 Model of Severe Pulmonary Arterial Hypertension Related to Failure of Right Ventricular Adaptation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Colin Suen ◽  
Baohua Jiang ◽  
Yupu Deng ◽  
Mohamad Taha ◽  
Ketul Chaudhary ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
High Mortality ◽  
Systolic Pressure ◽  
Sd Rats ◽  
Pulmonary Arterial ◽  
Fischer Rats ◽  
Severe Pulmonary Arterial Hypertension

Introduction: Inhibition of VEGFR2 with SU5416 (SU) in combination with chronic hypoxia (CH), produces severe pulmonary arterial hypertension (PAH) in rats with complex arterial remodeling that closely resembles plexiform lesions typical of human PAH. Survival in severe PAH is related to the ability of the right ventricle (RV) to adapt to increased afterload. In this study, we explored the effect of genetic background on right ventricular adaptation and survival in the Methods: PAH was induced by a single subcutaneous injection of SU5416 (20mg/kg) in 6-week old Sprague-Dawley (SD, Harlan, USA) or Fischer rats (CDF, Charles River), followed by a 3-week exposure to CH (10% O2). RV structure and function was assessed by echocardiography (Vevo 2100, Visual Sonics) and cardiac MRI (Agilent 7.0T). Exercise capacity was evaluated at 4 weeks post-SU by treadmill testing. At end study (4 or 7 weeks post-SU), right ventricular systolic pressure (RVSP) was assessed by right heart catheterization. Results: SD and Fischer rats exhibited in similar elevations in RVSP (104± 13 vs 102 ±6 mmHg, respectively), number of occlusive pulmonary vascular lesions and RV hypertrophy (RV/LV+S) in response to SU/CH. However, Fischer rats exhibited markedly higher mortality, with only 27% surviving to 7 weeks compared with 100% survival in SD rats (p<0.01), which was associated with significantly greater RV dilatation (RV/LV end diastolic diameter: 2.16 ± 0.24 vs. 1.19 ± 0.09 mm, p<0.001) at 4 weeks post-SU (Figure 1). Additionally, RV capillary density (516 ± 55 vs 786 ± 38 capillaries/mm2) and exercise capacity (treadmill distance, 59 ± 29 vs 210 ± 52 m, p<0.05) were also significantly reduced in Fischer vs SD SU/CH rats. Conclusions: These data suggest that the high mortality in Fischer compared to SD rats in the SU/CH model of severe PAH is related to a strain-dependent abnormality in RV adaptation at least in part due to lack of adequate microvascular angiogenesis in the hypertrophied RV.

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.

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