title: Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans.
abstract: The low barometric pressure at high altitude causes lower arterial oxygen content among Tibetan highlanders, who maintain normal levels of oxygen use as indicated by basal and maximal oxygen consumption levels that are consistent with sea level predictions. This study tested the hypothesis that Tibetans resident at 4,200 m offset physiological hypoxia and achieve normal oxygen delivery by means of higher blood flow enabled by higher levels of bioactive forms of NO, the main endothelial factor regulating blood flow and vascular resistance. The natural experimental study design compared Tibetans at 4,200 m and U.S. residents at 206 m. Eighty-eight Tibetan and 50 U.S. resident volunteers (18-56 years of age, healthy, nonsmoking, nonhypertensive, not pregnant, with normal pulmonary function) participated. Forearm blood flow, an indicator of systemic blood flow, was measured noninvasively by using plethysmography at rest, after breathing supplemental oxygen, and after exercise. The Tibetans had more than double the forearm blood flow of low-altitude residents, resulting in greater than sea level oxygen delivery to tissues. In comparison to sea level controls, Tibetans had >10-fold-higher circulating concentrations of bioactive NO products, including plasma and red blood cell nitrate and nitroso proteins and plasma nitrite, but lower concentrations of iron nitrosyl complexes (HbFeIINO) in red blood cells. This suggests that NO production is increased and that metabolic pathways controlling formation of NO products are regulated differently among Tibetans. These findings shift attention from the traditional focus on pulmonary and hematological systems to vascular factors contributing to adaptation to high-altitude hypoxia.
authors.affiliation: Department of Pathobiology, Allergy, and Critical Care, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: A J
authors.initials: AJ
authors.lastname: Janocha
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Bauer
authors.forename: N S
authors.initials: NS
authors.lastname: Bryan
authors.forename: J
authors.initials: J
authors.lastname: Tejero
authors.forename: C
authors.initials: C
authors.lastname: Hemann
authors.forename: R
authors.initials: R
authors.lastname: Hille
authors.forename: D J
authors.initials: DJ
authors.lastname: Stuehr
authors.forename: M
authors.initials: M
authors.lastname: Feelisch
authors.forename: C M
authors.initials: CM
authors.lastname: Beall
mesh_terms: D000531:Altitude; D001783:Blood Flow Velocity; D001827:Body Height; D004730:Endothelium, Vascular / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000209:etiology; D009569:Nitric Oxide / Q000097:blood*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D011312:Pressure; D012016:Reference Values; D018609:Tibet; D014655:Vascular Resistance
chemical_list: D009569:Nitric Oxide; D010100:Oxygen