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 microvasculature in a blister base raised on the hind footpad. Superfusion of substance P (1 microM) over the blister base caused an increase in plasma extravasation and a vasodilator response which was not maintained. N(G)-Nitro-L-arginine (100 microM), 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. Neurokinin A (1 microM), 5-hydroxytryptamine (1 microM), ATP (50 microM) and vasoactive intestinal polypeptide (1 microM) elicited vasodilation, which for vasoactive intestinal polypeptide was maintained even after washout. 5-Hydroxytryptamine and neurokinin A, but not ATP or vasoactive intestinal polypeptide, significantly increased plasma extravasation. Vasodilatation to neurokinin A, 5-hydroxytryptamine and ATP, and the increase in plasma extravasation due to neurokinin A and 5-hydroxytryptamine were unaffected by N(G)-nitro-L-arginine (100 microM), whereas vasodilation due to vasoactive intestinal polypeptide was significantly attenuated. 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 the plasma extravasation induced by neurokinin A or 5-hydroxytryptamine.
Ralevic
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V
Department of Anatomy and Developmental Biology, University College London, UK.
Khalil
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Helme
R D
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Dusting
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GJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D005260:Female; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D018836:Inflammation Mediators; D018040:Receptors, Neurokinin-1; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D013373:Substance P; D015288:Neurokinin A; D000255:Adenosine Triphosphate; D001120:Arginine