RGD Reference Report - Nitric oxide synthase 3-dependent vascular remodeling and circulatory dysfunction in cirrhosis. - Rat Genome Database

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Nitric oxide synthase 3-dependent vascular remodeling and circulatory dysfunction in cirrhosis.

Authors: Fernandez-Varo, G  Ros, J  Morales-Ruiz, M  Cejudo-Martin, P  Arroyo, V  Sole, M  Rivera, F  Rodes, J  Jimenez, W 
Citation: Fernandez-Varo G, etal., Am J Pathol. 2003 Jun;162(6):1985-93.
RGD ID: 7794774
Pubmed: PMID:12759254   (View Abstract at PubMed)
PMCID: PMC1868141   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)64331-3   (Journal Full-text)

Vascular remodeling is an active process that consists in important modifications in the vessel wall. Endothelium-derived nitric oxide (NO) plays a major role in this phenomenon. We assessed wall thickness (WT), total wall area (TWA), lumen diameter, and total nuclei number/cross-section (TN) in cirrhotic rats with ascites and in control rats. A second group of cirrhotic rats received the NO synthesis inhibitor, L-NAME, or vehicle daily for 11 weeks and systemic hemodynamics, arterial compliance, aortic NO synthase 3 (NOS3) protein expression, and vascular morphology were analyzed. Cirrhotic vessels showed a significant reduction in WT, TWA, and TN as compared to control vessels. Long-term inhibition of NOS activity in cirrhotic rats resulted in a significant increase in WT, TWA, and TN as compared to cirrhotic rats receiving vehicle. NOS3 protein abundance was higher in aortic vessels of nontreated cirrhotic animals than in controls. This difference was abolished by chronic treatment with L-NAME. NOS inhibition in cirrhotic rats resulted in higher arterial pressure and peripheral resistance and lower arterial compliance than cirrhotic rats receiving vehicle. Therefore, vascular remodeling in cirrhosis with ascites is a generalized process with significant functional consequences that can be negatively modulated by long-term inhibition of NOS activity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
liver cirrhosis treatmentISONos3 (Rattus norvegicus)7794774; 7794774 RGD 
liver cirrhosis treatmentIDA 7794774 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information