DIFFERENTIAL-EFFECTS OF L-N-5-(1-IMINOETHYL)-ORNITHINE ON TONE AND ENDOTHELIUM-DEPENDENT VASODILATOR RESPONSES

The effects of the nitric oxide (NO) synthesis inhibitor L-N-5-(1-imin oethyl)-ornithine (L-NIO) on baseline tone and on responses to the end othelium-dependent vasodilator agents were investigated in the pulmona ry vascular bed of the cat under constant-flaw conditions. When admini stered in doses of 1 and 5 mg/kg iv, L-NIO inhibited pulmonary vasodil ator responses to acetylcholine, bradykinin, and substance P but did n ot alter vasodilator responses to adenosine, pinacidil, or adrenomedul lin. L-NIO in doses of 1-10 mg/kg iv did not significantly affect base line lobar arterial pressure, and when administered in doses of 10-30 mg/kg iv the inhibitory effect on responses to bradykinin and substanc e P was not greater than that observed when the lower doses of L-NIO w ere administered. L-NIO in doses of 5-30 mg/kg iv reduced plasma react ive nitrogen intermediate levels. The inhibitory effects of L-NIO were similar to the inhibitory effects of N-omega-nitro-L-arginine, N-omeg a-nitro-L-arginine methyl eater, and NO-nitro-L-arginine benzyl ester. The highest dose of L-NIO studied (30 mg/kg iv) caused a significant increase in lobar arterial pressure, and the administration of N-omega -nitro-L-arginine methyl ester (100 mg/kg iv) caused a significant inc rease in lobar arterial pressure in animals previously treated with L- NIO (1 mg/kg iv). The results of the present study show that the effec ts of L-NIO on endothelium-dependent vasodilator responses and on base line tone can be separated and may be interpreted to suggest that basa l release of NO does not play an important role in the maintenance of baseline tone in the pulmonary vascular bed of the cat.