ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN REACTIVE HYPEREMIA IN CANINE DIAPHRAGM

We studied the effect of N(G)-nitro-L-arginine (L-NA) on reactive hype remia in the vascularly isolated hemidiaphragm of anesthetized dogs pr etreated with indomethacin. In nine animals, the diaphragm was autoper fused from the left femoral artery. Phrenic arterial flow was interrup ted for 10120 s during a control period and after 20 min of L-NA infus ion (6 x 10(-4) M). Postocclusive flow and duration of hyperemia durin g the control period increased progressively with increasing occlusion duration. After L-NA infusion, baseline and postocclusive flow in res ponse to all occlusions declined significantly compared with control v alues. However, when normalized as percentage of baseline flow, postoc clusive flow remained similar to that during the control period. By co mparison, the duration of reactive hyperemia was significantly shorten ed by L-NA infusion. In five animals, we repeated the same protocol du ring pump perfusion of the diaphragm at a fixed flow rate. L-NA infusi on increased baseline and postocclusive phrenic resistance in response to all occlusion durations; however, postocclusive phrenic resistance as percentage of baseline remained similar to control values. In addi tion, hyperemia durations in response to 60- and 120-s occlusions were shortened significantly by L-NA infusion. We conclude that 1) endothe lium-derived relaxing factor plays an important role in the regulation of baseline vasomotor tone in the diaphragm and 2) modulation of endo thelium-derived relaxing factor release contributes to the reactive va sodilatory response to transient vascular occlusion in the diaphragm.