NITRIC-OXIDE AND ENDOTHELIUM-DEPENDENT RELAXATION IN TRACHEOBRONCHIALLYMPH VESSELS

Lymphatic smooth muscle tone and contractility are important determina nts of lymph flow. Because we have shown previously that lymph vessels exhibit endothelium-dependent relaxation similar to that identified i n blood vessels, we assessed the possible role of nitric oxide as an e ndothelium-dependent relaxant factor in lymph vessels using porcine tr acheobronchial lymph vessel rings mounted in organ baths. Isometric ac tive tension was measured and normalized as a percentage of response t o 65 mM KCl-substituted perfusate. Histamine and NE elicited contracti on in all vessel rings at a concentration of 10(-5) M, and we were una ble to demonstrate relaxant responses to these substances even at low concentrations. In histamine- and NE-contracted vessel rings an increa se in active tension was produced by NMMA (33.9 +/- 5.4 and 26.1 +/- 5 %, respectively, P < 0.0001 for each), an effect that was reversed by addition of L-arginine but not by D-arginine. Endothelial disruption r eversed the effects of NMMA in histamine-contracted (16.2 +/- 4.0% inc rease in active tension; P = N.S. vs initial histamine response) and i n NE-contracted vessel rings (11.5 +/- 1.2% increase in active tension ; P = N.S. vs initial NE response). The data provide evidence that nit ric oxide is an endothelium-dependent relaxant factor that regulates t racheobronchial lymphatic smooth muscle tone and is released in respon se to administration of contractile agonists. (C) 1994 Academic Press, Inc.