RGD Reference Report - Involvement of Rho kinase in the pathogenesis of acute pulmonary embolism-induced polystyrene microspheres in rats. - Rat Genome Database

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Involvement of Rho kinase in the pathogenesis of acute pulmonary embolism-induced polystyrene microspheres in rats.

Authors: Toba, M  Nagaoka, T  Morio, Y  Sato, K  Uchida, K  Homma, N  Takahashi, K 
Citation: Toba M, etal., Am J Physiol Lung Cell Mol Physiol. 2010 Mar;298(3):L297-303. doi: 10.1152/ajplung.90237.2008. Epub 2009 Nov 13.
RGD ID: 7240517
Pubmed: (View Article at PubMed) PMID:19915157
DOI: Full-text: DOI:10.1152/ajplung.90237.2008

Acute pulmonary embolism (PE) is a life-threatening disease, and several vasoconstrictors, including endothelin-1 (ET-1), play a key role in vasoconstriction and hypoxemia during the development of PE. Rho kinase is activated by various vasoconstrictors resulting in vascular contraction and remodeling. Recent evidence has revealed an important role of Rho kinase in the pathogenesis of systemic and pulmonary vascular diseases. However, contribution of Rho kinase in PE remains unclear. We thus investigated the role of Rho kinase in the PE rat model induced by intrajugular administration of polystyrene microspheres (mean diameter, 26 microm). At 6 h following the administration of microspheres (1.5 ml/kg), right ventricular systolic pressure (RVSP) was higher in the PE than in the control rats (15.8 +/- 1.6 vs. 32.9 +/- 7.5 mmHg). Arterial oxygen tension was lower (92.3 +/- 12.5 vs. 66.0 +/- 17.7 Torr), and alveolar-arterial difference in oxygen partial pressure was higher (3.9 +/- 3.8 vs. 36.5 +/- 26.9 Torr) in the PE rats. Western blotting analysis revealed upregulation and downregulation in expression of vascular cell adhesion molecule-1 and endothelial nitric oxide synthase in lungs from the PE rats, respectively, and radioimmunoassay demonstrated an increase in plasma ET-1 levels. Lung Rho kinase alpha expression was greater in the PE rats. At 5 h following administration of microspheres (0.75 ml/kg), intravenous Rho kinase inhibitors HA1077 and Y27632 (3 mg/kg each) attenuated elevation of RVSP (22.0 +/- 3.7, 17.1 +/- 3.2, 14.3 +/- 2.6 mmHg, PE, PE+HA1077, PE+Y27632) and the severity of hypoxemia (66.3 +/- 16.2, 94.9 +/- 23.0, 89.1 +/- 8.5 Torr, PE, PE+HA1077, PE+Y27632) in the PE rats. These results suggest that pulmonary endothelial dysfunction and activation of Rho kinase may contribute to the potentiation of vasoconstriction and hypoxemia in the PE rats.

Annotation

Disease Annotations    
pulmonary embolism  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Vcam1  (vascular cell adhesion molecule 1)

Genes (Mus musculus)
Vcam1  (vascular cell adhesion molecule 1)

Genes (Homo sapiens)
VCAM1  (vascular cell adhesion molecule 1)


Additional Information