Release of norepinephrine from adrenergic nerve endings of blood vessels is modulated by endothelium-derived relaxing factor.

The release of norepinephrine from adrenergic nerve endings is inhibited by substances which raise cyclic 3',5'-guanosine monophosphate (cGMP) in neural tissue. Endothelium-derived relaxing factor (EDRF) elevates cGMP in vascular smooth muscle. Thus, EDRF may also modulate the release of norepinephrine (NE) from adrenergic nerves. We tested this postulate in isolated canine pulmonary arteries and veins using the technique of superfusion and measurement of the efflux of radiolabeled NE during transmural nerve stimulation at 1, 2, 4, 8, 16 and 32 Hz for 10 min. In segments of artery and vein with intact endothelium the contractile responses to low frequency nerve stimulation were decreased when compared to endothelium rubbed blood vessels. Electrical stimulation of arteries and veins with intact endothelium for 10 min released less 2-[14C]-NE than rubbed blood vessels, especially at the lower frequencies of 1, 2 and 4 Hz, with lesser effects at frequencies of 16 and 32 Hz. Using the technique of bioassay, EDRF from porcine thoracic aorta inhibited the efflux of 2-[14C]-NE from the pulmonary artery and vein. The findings support the conclusion that the endothelium can inhibit release of NE from sympathetic nerve innervating canine pulmonary artery and vein. The endothelium, in part through EDRF, can act as an endogenous inhibitor or sympathetic neurotransmitter release.