Sending a Signal through a Gas

The discovery of nitric oxide as a signaling molecule began with studies on the mechanism by which blood vessels relax and constrict, processes known as vasodilation and vasoconstriction. In addition to their desire to understand the basic biology of these processes, scientists recognized its medical importance, as drugs that promote vasodilation could aid in the treatment of cardiovascular diseases. Nitroglycerin, long used to treat angina pectoris, was known to promote vasodilation. When applied to isolated blood vessels, nitroglycerin and other nitrogen-containing compounds had been found to activate a signaling pathway that began by stimulating the production of cyclic guanosine monophosphate (cGMP), and eventually resulted in dilation. There was much interest in discovering the natural signal for this process. In vivo, vasodilation was known to occur after stimulation of vessels by the neurotransmitter acetylcholine. However, uncovering the mechanism of this response was hindered by a puzzling finding by Robert Furchgott. In his research on the constriction and relaxation of blood vessels, Furchgott was using isolated rabbit aorta as a model system. He found that adding the neurotransmitter acetylcholine to section of isolated rabbit aorta in vitro caused SENDING A SIGNAL THROUGH A GAS