COMPARISON OF FOREARM VASODILATATION TO SUBSTANCE-P AND ACETYLCHOLINE- CONTRIBUTION OF NITRIC-OXIDE

1. Forearm blood how responses to incremental challenges of acetylchol ine and substance I: administered via the brachial artery, were measur ed by venous occlusion plethysmography in eight subjects in the presen ce of saline, the nitric oxide synthase inhibitor, N-G-monomethyl-L-ar ginine, and a control vasoconstrictor, noradrenaline. 2. Substance P a nd acetylcholine caused dose-dependent increases in forearm blood flow (P < 0.001). When separated by 30 min saline infusions, repeated resp onses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean re duction in basal blood how of 34-51% (P < 0.001), and augmented the pe rcentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions. 4. N-G-Monomethyl-L-arginine cause d a mean reduction in basal blood flow of 42-45% (P < 0.001) and signi ficantly inhibited the responses to both substance P (P < 0.001) and a cetylcholine (P = 0.05). 5. In comparison with saline responses, N-G-m onomethyl-L-arginine caused a mean inhibition of 69 +/- 8% for substan ce P-induced vasodilatation and 40 +/- 5% for acetylcholine-induced va sodilatation. However comparing responses with those to the control va soconstrictor noradrenaline, N-G-monomethyl-L-arginine caused a mean i nhibition of 81 +/- 5% for substance P responses and 58 +/- 3% for ace tylcholine responses. Inhibition by N-G-monomethyl-L-arginine of the r esponse to substance P was significantly greater than inhibition of th e response to acetylcholine (P = 0.02). 6. Hence, in healthy men, a gr eater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater s tability, substance P may be more suitable as a pharmacological tool i n the investigation of stimulated nitric oxide production and endothel ial cell function.