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Marked Strain-Specific Differences in the SU5416 Rat Model of Severe Pulmonary Arterial Hypertension.
Jiang, Baohua; Deng, Yupu; Suen, Colin; Taha, Mohamad; Chaudhary, Ketul R; Courtman, David W; Stewart, Duncan J.
Afiliación
  • Jiang B; 1 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and.
  • Deng Y; 1 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and.
  • Suen C; 1 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and.
  • Taha M; 2 Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
  • Chaudhary KR; 1 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and.
  • Courtman DW; 2 Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
  • Stewart DJ; 1 Sinclair Centre for Regenerative Medicine, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and.
Am J Respir Cell Mol Biol ; 54(4): 461-8, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26291195
We assessed the pulmonary hemodynamic response to vascular endothelial growth factor receptor, type 2, inhibition using SU5416 (SU) with and without chronic hypoxia (CH) in different background strains and colonies of rats. A single subcutaneous injection of SU (20 mg/kg) or vehicle was administered to different substrains of Sprague-Dawley (SD) rats, and they were compared with Lewis and Fischer rats, with and without exposure to CH (10% O2 for 3 wk). Remarkably, a unique colony of SD rats from Charles River Laboratories, termed the SD-hyperresponsive type, exhibited severe pulmonary arterial hypertension (PAH) with SU alone, characterized by increased right ventricular systolic pressure, right ventricular/left ventricular plus septal weight ratio, and arteriolar occlusive lesions at 7-8 weeks (all P < 0.0001 versus vehicle). In contrast, the other SD substrain from Harlan Laboratories, termed SD-typical type, as well as Fischer rats, developed severe PAH only when exposed to SU and CH, whereas Lewis rats showed only a minimal response. All SD-typical type rats survived for up to 13 weeks after SU/CH, whereas SD-hyperresponsive type rats exhibited mortality after SU and SU/CH (35% and 50%, respectively) at 8 weeks. Fischer rats exposed to SU/CH exhibited the greatest mortality at 8 weeks (78%), beginning as early as 4 weeks after SU and preceded by right ventricle enlargement. Of note, a partial recovery of PAH after 8 weeks was observed in the SD-typical type substrain only. In conclusion, variation in strain, even between colonies of the same strain, has a remarkable influence on the nature and severity of the response to SU, consistent with an important role for genetic modifiers of the PAH phenotype.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Modelos Animales de Enfermedad / Hipertensión Pulmonar / Indoles Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Modelos Animales de Enfermedad / Hipertensión Pulmonar / Indoles Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Respir Cell Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos