Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated neonatal guinea pig lung.
Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, has been previously identified in the pulmonary and systemic vasculature of the newborn guinea pig using isolated arterial rings. The aim of our study was to determine if EDRF regulates vasomotor tone at the level of resistance vessels in the neonatal pulmonary circulation. Isolated lungs from guinea pigs (1-3 d old, n = 4-8/protocol) were ventilated with room air and perfused with a Krebs-Henseleit solution containing albumin at a constant flow. Angiotensin II (AII, 6 nM) was added to the perfusate to give a stable elevation in mean pulmonary artery pressure (PAP) from 7.0 +/- 1.1 to 19.7 +/- 1.5 torr, a 182 +/- 32% (mean +/- SEM) increase above baseline. Addition of bradykinin (BK, 10 nM) or L-arginine (2 mM) markedly reduced the AII-induced elevation in PAP. At the steady state response to BK (33% above baseline), addition of Hb (10 microM, binds EDRF), NG-monomethyl-L-arginine (NMA, 100 microM, blocks EDRF production), NMA (200 microM), or NMA + Hb, reversed the effect of BK to the following levels of PAP above baseline: 77 +/- 5, 94 +/- 24, 163 +/- 20, or 246 +/- 25%, respectively (p less than 0.05). Indomethacin had no effect on BK-induced vasodilation. In separate studies, NMA (200 microM) increased baseline PAP by 46 +/- 13% and NMA pretreatment raised the AII-pressor response (AII 6 nM) from 133 +/- 49 to 306 +/- 65% above baseline PAP.(ABSTRACT TRUNCATED AT 250 WORDS)
Davidson
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Division of Neonatal-Perinatal Medicine, Schneider Children's Hospital, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Eldemerdash
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D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D001920:Bradykinin