Regulation of nitric oxide synthase gene expression by cytokines.
Evidence is presented that not only macrophage type of NO synthase but also endothelial constitutive type of NO synthase genes are regulated by a variety of exogenous stimuli including cytokines. It is possible that pathophysiological concentrations of TNF-alpha noted in some patients with congestive heart failure may be sufficient to decrease levels for the constitutive form of NO synthase and increase those for the inducible form of NO synthase. Interestingly, chronic exercise in dogs was demonstrated to increases coronary vascular NO production and steady-state mRNA levels of ecNO synthase. Endogenous NO plays a crucial role in modulating vascular tone and inhibiting interactions of the vessel wall with circulating blood elements such as platelets, monocytes and neutrophils. It is possible that alterations in its synthesis or activity may play an important role in some cardiovascular disorders including congestive heart failure. Further studies of the pathophysiological significance of NO in specific experimental and clinical settings of congestive heart failure may provide a basis for improved therapeutic measures to enhance the synthesis or effect of endogenous NO, or to supplement its activity with exogenous NO donors or superoxide scavengers.
Yokoyama
M
M
First Department of Medicine, Kobe University School of Medicine, Japan.
Hirata
K
K
Kawashima
S
S
Kawahara
Y
Y
D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology; D016207:Cytokines / Q000502:physiology*; D004285:Dogs; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics*
D016207:Cytokines; D019001:Nitric Oxide Synthase