Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation.
Nerve-induced vasodilatation was studied by intravital microscopy of the rabbit tenuissimus muscle, pretreated with pancuronium, phentolamine, and guanethidine. Nerve stimulation of the tenuissimus nerve induced a vasodilatation which was frequency and pulse duration-dependent and insensitive to atropine and propanolol but abolished by tetrodotoxin. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not its enantiomer, D-NAME, markedly inhibited the vasodilation induced by nerve stimulation or by exogenous substance P or neurokinin A. Vasodilatation due to calcitonin gene-related peptide, prostaglandin E2 or nitroprusside was unaffected. The substance P antagonist, spantide (30 microM), significantly attenuated nerve-induced vasodilatation, in parallel with L-NAME. Our results indicate that nerve-induced vasodilatation in skeletal muscle can be attributed to the release of substance P and/or other tachykinins and that nitric oxide subsequently mediates the response to endogenous tachykinins released from nerves.
Persson
M G
MG
Department of Physiology, Karolinska Institutet, Stockholm, Sweden.
Hedqvist
P
P
Gustafsson
L E
LE
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006614:Hindlimb; D006940:Hyperemia / Q000209:etiology; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D015288:Neurokinin A / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010197:Pancuronium / Q000494:pharmacology; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D015320:Tachykinins; D009569:Nitric Oxide; D013373:Substance P; D001285:Atropine; D015288:Neurokinin A; D001120:Arginine; C053010:NPC 567; D010197:Pancuronium; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester