The Molecular Basis of the Interplay between Endothelin-1 and Nitric Oxide and its Relevance for Atherosclerosis and Arterial and Pulmonary Hypertension

Author(s): Teresa M. Seccia, Giuseppe Maiolino, Achille C Pessina, Gian Paolo Rossi

Journal Name: Vascular Disease Prevention (Discontinued)

Volume 2 , Issue 1 , 2005


Nitric oxide (NO) and endothelin-1 (ET-1) are the prototype of endothelium-derived relaxing (EDRFs) and constricting factors (EDCFs), respectively. They have been studied extensively in relation to cardiovascular disease, but there is limited information on their interaction. Nonetheless, compelling evidence indicates that in several conditions with excess cardiovascular risk, blunted NO affects are coupled with enhanced ET-1 synthesis, thus suggesting a reciprocal regulation of these two factors. Consistent with this contention is the evidence that NO inhibits the synthesis of ET-1 in different cell types and that ET-1 blunts NO release in response to stimulation by cytokines. However, it is likely that ET-1 can play an ambivalent role since it enhances NO release, both directly, via ETB receptors on endothelial cells, and indirectly, by causing vasoconstriction and, thereby, increasing laminar shear stress. A number of in vitro and in vivo studies have unravelled the complexity of the mechanisms underlying the regulation of NO and ET-1 synthesis. Several factors can affect in opposite directions the transcription of the NO synthase and preproET-1 genes. The family of NF-kB transcription factors, peroxisome proliferator-activated receptors and reactive oxygen species appear to play a major role in this regulation, as well as in triggering early events of atherogenesis. The purpose of this review is, therefore, to examine the molecular mechanisms regulating the interplay between NO and ET-1, and to discuss their implications for arterial and pulmonary hypertension, and for atherosclerosis.

Keywords: endothelin, nitric oxide, atherosclerosis, arterial hypertension, coronary artery disease, pulmonary hypertension

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Article Details

Year: 2005
Page: [53 - 66]
Pages: 14
DOI: 10.2174/1567270010502010053

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