Nitric oxide (NO) functions in biology as both a critical cytotoxic agent and an essential signaling molecule. The toxicity of the diatomic gas has long been accepted; however, it was not known to be a signaling molecule until it was identified as the endothelium-derived relaxing factor (EDRF). Since this discovery, the physiological signaling pathways that are regulated by NO have been the foc...

The identification of endothelium-derived relaxing factor as nitric oxide (NO) dramatically altered the course of vascular biology, as well as other biomedical disciplines. The ubiquity of this natural product of cell metabolism and the complexity of its biochemistry provide a rich source of molecular mediators of phenotype in health and disease.

Nitric oxide (NO) was among the first gases to be discovered. It was discovered by Joseph Priestley in 1772—two years after his discovery of oxygen (O2). For more than two centuries this colorless and odorless gas was considered highly toxic. Several chemists have died of what we now call toxic-shock syndrome, after purposely or accidentally inhaling large amounts of it. No one anticipated that...

A ctivation of endothelial cells by physical, chemical , and hormonal stimuli can result in the release of a number of vasoactive mediators.1 Under physiological conditions, mediator release appears to be balanced in favor of inhibitory factors such as endothelium-derived relaxing factor (EDRF, identified as nitric oxide) and prostacyclin (PGI2) (Figure 1).'-3 EDRF-NO and PGI have important pro...

We have dissociated the effects of frequency and amplitude of pulsatile flow on flow-induced release of endothelium-derived relaxing factor (EDRF) using cascade bioassay. Rat aortic segments were buffer perfused with a peristaltic pump at a constant mean flow rate of 9 ml/min. EDRF activity in effluent was measured by relaxation of endothelium-denuded rabbit aortic rings preconstricted by pheny...

The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells. Indeed, these cells can release both dilator and constrictor substances. The major endothelium-derived relaxing factor may be nitric oxide, which activates soluble guanylate cyclase in the smooth muscle, although the endothelial cells also secrete an unidentified hyperpo...

Nitric oxide was named “Molecule of the Year” in 1992 by the journal Science, but it took another 6 years for those responsible for the major discoveries surrounding it to win the Nobel Prize. Three US scientists—Robert F. Furchgott, PhD, Louis J. Ignarro, PhD, and Ferid Murad, MD, PhD—will receive the 1998 Nobel Prize for Physiology and Medicine on December 10, 1998, in Stockholm, Sweden. The ...

The mechanism of the inhibitory action of phenidone, 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C), dithiothreitol, hydroquinone, and pyrogallol on the vascular relaxation induced by endothelium-derived relaxing factor (EDRF) was investigated. EDRF was released from porcine aortic endothelial cells in culture and bioassayed on a cascade of superfused rabbit aortic strips. These c...

BACKGROUND The endothelium-derived relaxing factor has been shown to be nitric oxide or a related nitroso compound, synthesized by the enzyme nitric oxide synthetase, which oxidizes the guanidono nitrogens of arginine. This enzyme is activated by increases in cytosolic calcium. The effect of the clinically used calcium channel antagonists on this process is controversial. The present study was ...

The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells. Indeed, these cells can release both dilator and constrictor substances. The major endothelium-derived relaxing factor may be nitric oxide, which activates soluble guanylate cyclase in the smooth muscle, although the endothelial cells also secrete an unidentified hyperpo...