During the decades since Ignarro and Furchgott's initial research, thousands of studies have been published about the effects of nitric oxide as the endothelium derived relaxing factor.

In 1984 he realized that the properties of nitric oxide were the same as those seen in the endothelium derived relaxing factor previously-identified by Robert Furchgott 3 years earlier.

A reduced release of endothelium derived relaxing factor (EDRF) causes a decrease in the stimulation of guanylate cyclase and cyclic GMP (cGMP) levels fall in vascular smooth muscle.