Voltammetric and functional evidence that N-methyl-D-aspartate and substance P mediate rat vascular relaxation via nitrogen monoxide release.
It is known that substance P acts as a vasodilator via activation of the enzyme nitrogen monoxide synthase (NOS) in endothelial tissue and it is suggested that N-methyl-D-aspartate (NMDA) could stimulate nitrogen monoxide (NO) release within nervous tissue. However, the data reported concern NO metabolites (nitrites, nitrates), while there is no clear evidence to date of the action of the latter compound within the aortic tissue. In this study, amperometry with specifically prepared carbon fiber electrodes has been applied to examine the effect of NMDA or substance P upon NO release. In particular, the data obtained confirm that NMDA can stimulate NO release in vivo, in the striatum of anaesthetized rats, and that substance P can stimulate NO release in rat aortic rings (ex vivo experiments). In addition, they indicate that NMDA also stimulates NO release in rat aortic rings. This original data has been confirmed by the observation of a vasorelaxant action of NMDA within noradrenaline precontracted aortic rings. Thus, these experiments provide the first direct evidence that NMDA can mediate vascular relaxation via NO release.
Crespi
F
F
Department of Biology, Glaxo Wellcome S.p.A., Medicine Research Centre, Verona, Italy. FC20377@ggr.co.uk
Lazzarini
C
C
Andreoli
M
M
Vecchiato
E
E
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002244:Carbon; D004566:Electrodes; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D016202:N-Methylaspartate; D002244:Carbon; D019331:NG-Nitroarginine Methyl Ester