title: Tissue oxygenation modifies nitric oxide bioavailability.
abstract: OBJECTIVE
  Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide-induced vasodilation (nitrovasodilation) by oxygen.
  
  
  METHODS
  We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well-oxygenated renal cortex or in the physiologically hypoxemic outer medulla.
  
  
  RESULTS
  In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L-NAME. By contrast, in the outer medulla, NO signals paradoxically rose following NOS inhibition, known to intensify local hypoxia. Other manipulations that intensify outer medullary hypoxia (such as indomethacin or radiologic contrast media) increased local NO readings, while measures known to ameliorate outer medullary hypoxia (furosemide, L-arginine, hypotension) reduced regional NO readings.
  
  
  CONCLUSIONS
  Oxygen appears to modulate NO bioavailability, in particular, in tissues with low ambient pO2, perhaps through enhanced binding to oxygenated hemoglobin. It is proposed that this phenomenon may participate in physiological microvascular regulation, with hypoxemia enhancing NO concentration, while hyperoxemia resulting in accelerated NO removal.
authors.affiliation: Department of Medicine, Hadassah Hospital-Mt. Scopus and the Hebrew University Medical School, Jerusalem, Israel.
authors.forename: S N
authors.initials: SN
authors.lastname: Heyman
authors.forename: M
authors.initials: M
authors.lastname: Goldfarb
authors.forename: D
authors.initials: D
authors.lastname: Darmon
authors.forename: M
authors.initials: M
authors.lastname: Brezis
mesh_terms: D000818:Animals; D001682:Biological Availability; D007668:Kidney / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D008833:Microcirculation; D009569:Nitric Oxide / Q000493:pharmacokinetics*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide