Effects of hypoxia and vascular tone on endothelium-dependent and -independent responses in developing lungs.
Both increases and decreases in endothelium-derived nitric oxide (EDNO) activity have been described in the developing pulmonary vasculature. We hypothesized that differences in baseline vasomotor tone and/or oxygen tension may contribute to this variability. Pulmonary arterial dose responses to endothelium-dependent and -independent vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were measured in indomethacin-treated lungs of 1- to 2-day-old (2D) and 1-mo-old (1M) lambs. During 4% O2 ventilation, baseline pulmonary vascular resistance (PVR) and the dilator response to both ACh and SNP were greater in 2D lungs. However, when baseline PVR values were matched at both ages during either hypoxia or infusion of a thromboxane mimetic under normoxic conditions, developmental differences in ACh-induced vasodilation were minimal. Furthermore, hypoxia itself did not alter the responses to ACh in 2D lungs. In contrast, SNP caused greater vasodilation in 2D than in 1M lungs regardless of baseline PVR. These data and studies suggest that whereas high PVR enhances EDNO synthesis, responsiveness to ENDO decreases as synthesis of ENDO increases in developing lungs studied under basal conditions.
Gordon
J B
JB
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
Martinez
F R
FR
O'Donnell
D C
DC
Tod
M L
ML
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000008:administration & dosage; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000096:biosynthesis*; D009599:Nitroprusside / Q000008:administration & dosage; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011659:Pulmonary Gas Exchange; D012756:Sheep; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine