RGD Reference Report - Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat. - Rat Genome Database

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Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat.

Authors: Nagaoka, T  Gebb, SA  Karoor, V  Homma, N  Morris, KG  McMurtry, IF  Oka, M 
Citation: Nagaoka T, etal., J Appl Physiol. 2006 Mar;100(3):996-1002. Epub 2005 Dec 1.
RGD ID: 1642819
Pubmed: PMID:16322374   (View Abstract at PubMed)
DOI: DOI:10.1152/japplphysiol.01028.2005   (Journal Full-text)

The fawn-hooded rat (FHR) develops severe pulmonary hypertension (PH) when raised for the first 3-4 wk of life in the mild hypoxia of Denver's altitude (5,280 ft.). The PH is associated with sustained pulmonary vasoconstriction and pulmonary artery remodeling. Furthermore, lung alveolarization and vascularization are reduced in the Denver FHR. We have recently shown that RhoA/Rho kinase signaling is involved in both vasoconstriction and vascular remodeling in animal models of hypoxic PH. In this study, we investigated the role of RhoA/Rho kinase signaling in the PH of Denver FHR. In alpha-toxin permeabilized pulmonary arteries from Denver FHR, the contractile sensitivity to Ca2+ was increased compared with those from sea-level FHR. RhoA activity and Rho kinase I protein expression in pulmonary arteries of Denver FHR (10-wk-old) were higher than in those of sea-level FHR. Acute inhalation of the Rho kinase inhibitor fasudil selectively reduced the elevated pulmonary arterial pressure in Denver FHR in vivo. Chronic fasudil treatment (30 mg.kg-1.day-1, from birth to 10 wk old) markedly reduced the development of PH and improved lung alveolarization and vascularization in Denver FHR. These results suggest that Rho kinase-mediated sustained vasoconstriction, through increased Ca2+ sensitivity, plays an important role in the established PH and that RhoA/Rho kinase signaling contributes significantly to the development of PH and lung dysplasia in mild hypoxia-exposed FHR.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  ISORhoa (Rattus norvegicus)1642819; 1642819protein:altered localization:pulmonary arteryRGD 
pulmonary hypertension  IEP 1642819protein:altered localization:pulmonary arteryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Rhoa  (ras homolog family member A)

Genes (Mus musculus)
Rhoa  (ras homolog family member A)

Genes (Homo sapiens)
RHOA  (ras homolog family member A)


Additional Information