ROLE OF NITRIC-OXIDE IN THE ACTIONS OF SUBSTANCE-P AND OTHER MEDIATORS OF INFLAMMATION IN RAT SKIN MICROVASCULATURE

The role of nitric oxide in inflammatory responses to substance P and other mediators of inflammation was examined in rat skin microvasculat ure in a blister base raised on the hind footpad. Superfusion of subst ance P (1 mu M) over the blister base caused an increase in plasma ext ravasation and a vasodilator response which was not maintained. N-G-Ni tro-L-arginine (100 mu M), an inhibitor of nitric oxide biosynthesis, attenuated vasodilatation and plasma extravasation due to substance P. The inactive isomer N-G-nitro-D-arginine was without effect. Neurokin in A (1 mu M), 5-hydroxytryptamine (1 mu M) ATP (50 mu M) and vasoacti ve intestinal polypeptide (1 mu M) elicited vasodilatation, which for vasoactive intestinal polypeptide was maintained even after washout. 5 -Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intesti nal polypeptide, significantly increased plasma extravasation. Vasodil atation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine w ere unaffected by N-G-nitro-L-arginine (100 mu M), whereas vasodilatat ion due to vasoactive intestinal polypeptide was significantly attenua ted. These findings suggest that in rat skin microvasculature in vivo, nitric oxide is involved in vasodilator responses due to substance P and vasoactive intestinal polypeptide, and plasma extravasation due to substance P, but does not contribute significantly to vasodilatation induced by neurokinin A, 5-hydroxytryptamine or ATP, or to plasma extr avasation induced by neurokinin A or 5-hydroxytryptamine.