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PMID: 12652155 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The role of the NO axis and its therapeutic implications in pulmonary arterial hypertension.

Heart failure reviews ·Vol. 8 ·No. 1 ·2003-01-00 ·Pages 5-21

Michelakis ED

Abstract

Pulmonary Arterial Hypertension (PAH) is a disease of the pulmonary vasculature leading to vasoconstriction and remodeling of the pulmonary arteries. The resulting increase in the right ventricular afterload leads to right ventricular failure and death. The treatment options are limited, expensive and associated with significant side effects. The nitric oxide (NO) pathway in the pulmonary circulation provides several targets for the development of new therapies for this disease. However, the NO pathway is modulated at multiple levels including transcription and expression of the NO synthase gene, regulation of the NO synthase activity, regulation of the production of cyclic guanomonophosphate (cGMP) by phosphodiesterases, postsynthetic oxidation of NO, etc. This makes the study of the role of the NO pathway very difficult, unless one uses multiple complementary techniques. Furthermore, there are significant differences between the pulmonary and the systemic circulation which make extrapolation of data from one circulation to the other very difficult. In addition, the role of NO in the development of pulmonary hypertension varies among different models of the disease. This paper reviews the role of the NO pathway in both the healthy and diseased pulmonary circulation and in several animal models and human forms of the disease. It focuses on the role of recent therapies that target the NO pathway, including L-Arginine, inhaled NO, the phosphodiesterase inhibitor sildenafil and gene therapy.

MeSH Terms
Animals Humans Hypertension, Pulmonary/drug therapy,genetics,physiopathology Nitric Oxide/physiology,therapeutic use Nitric Oxide Synthase/genetics,metabolism Pulmonary Artery/metabolism,physiopathology Pulmonary Circulation/physiology Transcription, Genetic/genetics Vascular Resistance/physiology
Chemicals
Nitric Oxide Nitric Oxide Synthase
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Michelakis Evangelos D
University of Alberta Hospitals, Walter C McKenzie Health Sciences Centre, Edmonton, Canada. [email protected]
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Article Info
Journal
Heart failure reviews
Abbr.
Heart Fail Rev
ISSN
1382-4147
DOI
10.1023/a:1022150819223
Email
[email protected]
Published
2003-01-00
Pages
5-21
Language
English
Region
United States
NLM ID
9612481
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1022150819223 View journal details
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