The quantitative contribution of nitric oxide and sensory nerves to bradykinin-induced inflammation in rat skin microvasculature.
Using a blister model in the rat hind footpad, the present study undertook to examine the relative contribution of sensory nerves and nitric oxide (NO) to the inflammatory response induced by bradykinin (BK). Using this model, combined with laser Doppler flowmetry, we were able to simultaneously monitor two parameters of the inflammatory response, namely vasodilatation (VD) and plasma extravasation (PE). Perfusion of BK (1, 10 or 100 microM) over the blister base elicited both VD and PE responses which were dose-dependent. The VD response was of rapid onset, sustained at the lowest concentration (1 microM), and showed tachyphylaxis at the highest two concentrations (10 and 100 microM). The PE response, however, was delayed in onset at the lower concentration but the response was maintained at all concentrations. The endothelium-independent vasodilator, sodium nitroprusside. (SNP, 100 microM), was used as an internal control and elicited a rapid maintained VD response. In rats pretreated as neonates with capsaicin to destroy primary sensory afferents, the inflammatory response to 10 microM BK was significantly smaller (50% and 64% decrease in VD and PE, respectively). The selective inhibitor of NO synthase, NG-nitro-L-arginine (L-NORAG) at 100 microM significantly attenuated the inflammatory response to BK in control rats (76% and 60% decrease in VD and PE, respectively) with a further decrease in the response in capsaicin pretreated rats. The inactive stereoisomer NG-nitro-D-arginine (D-NORAG) (100 microM) did not affect the inflammatory response to BK. The vasodilator response to SNP was intact in capsaicin pretreated rats and was not affected by either L-NORAG or D-NORAG.(ABSTRACT TRUNCATED AT 250 WORDS)
Khalil
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National Research Institute of Gerontology and Geriatric Medicine, North West Hospital, Parkville, Vic., Australia.
Helme
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002211:Capsaicin; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D013237:Stereoisomerism
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002211:Capsaicin; D001920:Bradykinin