COMPARATIVE EFFECTS OF L-NNA AND ALKYL ESTERS OF L-NNA ON PULMONARY VASODILATOR RESPONSES TO ACH, BK, AND SP

The comparative effects of the nitric oxide (NO) synthase inhibitors N-omega-nitro-Larginine (L-NNA), N-omega-nitro-L-arginine methyl ester (L-NAME), and N-omega-nitro-L-arginine benzyl ester (L-NABE) on baseline tone and on vasodilator responses to acetylcholine (ACh), bradykinin (BK), and substance P (SP) were compared in the pulmonary vascular bed of the cat under constant flow conditions. After administration of the NO synthase inhibitors in intravenous doses of 100 mg/Bg, the increase in lobar arterial pressure and the attenuation of vasodilator responses to ACh, BK, and SP were similar, whereas responses to adenosine and felodipine, endothelium-independent vasodilator agents, were not altered. In addition to inhibiting responses to ACh, BK, and substance P, the NO synthase inhibitors enhanced vasodilator responses to S-nitroso-N-acetylpenicillamine and NO. Moreover, atropine inhibited pulmonary vasodilator responses to ACh but not to SP or BK, and L-NAME or L-NABE had no effect on the decrease in heart rate in response to efferent vagal stimulation, a muscarinic receptor-mediated response that is independent of NO release. The similar inhibitory effects of L-NNA, L-NAME, and L-NABE on vasodilator responses to ACh, BK, and SP suggest that the L-arginine analogue, L-NNA, as well as the methyl and benzyl esters of L-NNA are useful probes for studying NO-mediated endothelium-dependent responses in the pulmonary vascular bed of the intact-chest cat. The absence of an effect of L-NAME or L-NABE on the response to vagal stimulation suggests that the alkyl esters of L-NNA do not block muscarinic receptors in the cat.