title: Blood pressure response to hypoxia: role of nitric oxide synthase.
abstract: BACKGROUND
  Chronic exposure to hypobaric hypoxia has been shown to increase arterial pressure in genetically normal rats. The associated increase in blood pressure is unrelated to the hypoxia-induced erythrocytosis and persists indefinitely after restoration of normoxia. It is accompanied by a marked reduction in urinary excretion of nitric oxide metabolites (NOx) and is ameliorated by L-arginine supplementation. In view of the latter observations, we hypothesized that hypoxia-induced hypertension may be associated with downregulation of NO synthase (NOS).
  
  
  METHODS
  Male Sprague Dawley rats were randomized to the hypoxic and control groups. Rats assigned to the hypoxic group were placed in chambers with air pressure maintained at 390 mm Hg. Animals assigned to the control group were kept in the chamber at 760 mm Hg air pressure. Animals were kept in their respective conditions for up to 21 days. Group of animals were tested at days 2, 3, 7, and 21.
  
  
  RESULTS
  The hypoxic group exhibited a steady increase in arterial pressure beginning at day 3. This was accompanied by a transient increase followed by a significant decline in kidney NOS-I, NOS-II, and NOS-III abundance. A similar biphasic change was observed with NOS-II and NOS-III in the cardiac and vascular tissues. The changes in NOS abundance in the given tissues were associated with parallel changes in nitrotyrosine abundance, which reflects local NO production. The latter finding provides functional evidence for the changes observed in NOS abundance.
  
  
  CONCLUSIONS
  Chronic hypoxia-induced hypertension in rats is associated with marked downregulation of NOS isotypes, which can, in part, account for the previously reported L-arginine-responsive hypertension in this model.
authors.affiliation: Division of Nephrology and Hypertension, University of California, Irvine, Orange, California 92868, USA.
authors.forename: Cyril H
authors.initials: CH
authors.lastname: Barton
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Ni
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
mesh_terms: D000399:Air Pressure; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019001:Nitric Oxide Synthase