Is Nitric Oxide or a Prostaglandin the Endothelium-Derived Relaxing Factor in Fishes?

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Blood vessels in vertebrates have a thin lining of cells termed the endothelium, which was generally thought to provide little more than some protection against the adhesion of blood cells (RBCs, platelets, etc.) to the vascular smooth muscle which underlies the endothelium on the vessel wall. However, in recent years, it has become apparent that endothelial cells produce a variety of chemical messengers that no only protect against blood clotting but also control the diameter of the vessel itself by stimulating contraction or relaxation of the vascular smooth muscle. The most famous of these is the so-called "endothelium-derived relaxing factor", which is not thought to be nitric oxide. This gas is now considered to be the dominant EDRF in mammals, despite the fact that the endothelial cells produce other dilatory substances, such as the prostaglandins PGI2 and PGE. Dr. Evans' preliminary evidence has shown that this may not be the case in early vertebrates such as the dogfish shark. In this species, the endothelial nitric oxide system appears to be absent, and PGE, not PGI2, appears to be the only EDRF. The PI is interested in delineating the evolution of the EDRF control system, determining which it appeared and what role it plays in cardiovascular control in various groups of fishes. This NSF award will allow him to make these determinations.