CONTRIBUTIONS AND INTERACTIONS OF NITRIC OXIDE IN THE SKIN

Abstract

Nitric oxide (NO) is known to be a potent vasodilator throughout the circulation and has been shown to have a number of roles in the regulation of vascular tone in humans. During whole body heat stress, an elevation in core body temperature causes a reflex increase in skin blood flow that is partially dependent on NO. However, the exact role of NO in cutaneous active vasodilation is unclear. Animal research suggests that NO may play a “permissive” role in active vasodilation. That is, only a basal level of NO is required to allow full expression of active vasodilation mediated by an unknown neurotransmitter. In humans, we have found NO is not permissive for active vasodilation, but may act in a “synergistic” fashion. In this construct, NO and the unknown neurotransmitter may both directly mediate a portion of active vasodilation, but their combined effect is greater than the sum of their independent actions. This interaction may occur at the nerve where NO pre-junctionally enhances release of the unknown neurotransmitter or at the level of the second messenger systems. Of the main candidates for the putative vasodilator, vasoactive intestinal peptide (VIP) has been found to interact with NO in a synergistic manner in some animal tissues. Along these lines, we recently determined that NO-synthase inhibition blunts the vasodilator response to VIP in human skin; however, it is not yet known whether NO and VIP interact in a synergistic fashion. NO may interact with other neurotransmitters in the skin as well. For example, evidence suggests that NO may interact with various neurotransmitters released during direct heating of the skin, activation of the axon reflexes, pain sensation, and inflammation. Current research is directed towards understanding the complex interactions between NO and vasoactive substances in the regulation of cutaneous vascular tone. Supported by NIH HL70928, AHA 0265260Z