ROLE OF NITRIC-OXIDE TOWARDS VASODILATOR EFFECTS OF SUBSTANCE-P AND ATP IN HUMAN FOREARM VESSELS

1. It has been shown in animals that substance P as well as acetylchol ine releases endothelium-derived nitric oxide and evokes vasodilatatio n and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effect s of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a stra in-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery befo re and after infusion of N-G-monomethyl-L-arginine (4 or 8 mu mol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of L-arginine (10 mg/min, simu ltaneously), or before and Ih after oral administration of indomethaci n (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. N-G-Monomethy l-L-arginine decreased basal forearm blood how and inhibited acetylcho line-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation o f L-arginine nor pretreatment with indomethacin affected substance P-i nduced vasodilatation. 4. Our results suggest that, in the human forea rm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatat ion may also not be mediated by nitric oxide.