Flow-induced release of EDRF in the pulmonary vasculature: site of release and action.
Pulsatile flow is thought to lower pulmonary vascular resistance by passive recruitment of capillaries and by active vasodilation. This study was undertaken to investigate the role of endothelium-derived relaxing factor (EDRF) during pulsatile flow in isolated canine left lower lobes pretreated with indomethacin. The lobes were perfused in situ with autologous blood (approximately 500 ml/min) using a nonpulsatile pump (Masterflex) or a pulsatile pump (Harvard). With the occlusion techniques, vascular resistance was partitioned into four segments: arterial (Ra), small arterial (R'a), small venous, and venous (Rv). Pulsatile flow (frequency = 70 min-1) did not lower total vascular resistance during baseline or during vasoconstriction. Distribution of vascular resistance among the four segments was not altered significantly by pulsatile flow during normoxia and angiotensin. In contrast, switching to pulsatile flow during hypoxia was associated with an increase in Ra and a decrease in R'a and Rv. N omega-nitro-L-arginine (L-NNA) had no effect on total or segmental resistance during baseline conditions but potentiated the hypoxic pressor response and prevented its recovery by 50%. In addition, the reduction in R'a by pulsatile flow was attenuated by L-NNA, suggesting that EDRF is released by pulsatile flow in this segment. We conclude that a shear stress-induced EDRF release from the small arteries is present in canine lungs and is experimentally demonstrable during pulsatile flow and hypoxia.
Hakim
T S
TS
Department of Surgery, State University of New York Health Science Center, Syracuse 13210.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000378:metabolism; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D011652:Pulmonary Circulation / Q000502:physiology*; D011673:Pulsatile Flow; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000187:drug effects
D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin