Comparison of forearm vasodilatation to substance P and acetylcholine: Contribution of nitric oxide

1. Forearm blood how responses to incremental challenges of acetylcholine and substance I: administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, N-G-monomethyl-L-arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dose-dependent increases in forearm blood flow (P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean reduction in basal blood how of 34-51% (P < 0.001), and augmented the percentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions. 4. N-G-Monomethyl-L-arginine caused a mean reduction in basal blood flow of 42-45% (P < 0.001) and significantly inhibited the responses to both substance P (P < 0.001) and acetylcholine (P = 0.05). 5. In comparison with saline responses, N-G-monomethyl-L-arginine caused a mean inhibition of 69 +/- 8% for substance P-induced vasodilatation and 40 +/- 5% for acetylcholine-induced vasodilatation. However comparing responses with those to the control vasoconstrictor noradrenaline, N-G-monomethyl-L-arginine caused a mean inhibition of 81 +/- 5% for substance P responses and 58 +/- 3% for acetylcholine responses. Inhibition by N-G-monomethyl-L-arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine (P = 0.02). 6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.