Nitric oxide and endothelium-dependent relaxation in tracheobronchial lymph vessels

Lymphatic smooth muscle tone and contractility are important determinants of lymph flow. Because we have shown previously that lymph vessels exhibit endothelium-dependent relaxation similar to that identified in blood vessels, we assessed the possible role of nitric oxide as an endothelium-dependent relaxant factor in lymph vessels using porcine tracheobronchial lymph vessel rings mounted in organ baths. Isometric active tension was measured and normalized as a percentage of response to 65 mM KCl-substituted perfusate. Histamine and NE elicited contraction in all vessel rings at a concentration of 10(-5) M, and we were unable to demonstrate relaxant responses to these substances even at low concentrations. In histamine- and NE-contracted vessel rings an increase 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 reversed the effects of NMMA in histamine-contracted (16.2 +/- 4.0% increase in active tension; P = N.S. vs initial histamine response) and in NE-contracted vessel rings (11.5 +/- 1.2% increase in active tension; P = N.S. vs initial NE response). The data provide evidence that nitric oxide is an endothelium-dependent relaxant factor that regulates tracheobronchial lymphatic smooth muscle tone and is released in response to administration of contractile agonists.