title: Chronic hypoxia attenuates nitric oxide-dependent hemodynamic responses to acute hypoxia.
abstract: Alterations in the nitric oxide (NO) pathway have been implicated in the pathogenesis of chronic hypoxia-induced pulmonary hypertension. Chronic hypoxia can either suppress the NO pathway, causing pulmonary hypertension, or increase NO release in order to counteract elevated pulmonary arterial pressure. We determined the effect of NO synthase inhibitor on hemodynamic responses to acute hypoxia (10% O(2)) in anesthetized rats following chronic exposure to hypobaric hypoxia (0.5 atm, air). In rats raised under normoxic conditions, acute hypoxia caused profound systemic hypotension and slight pulmonary hypertension without altering cardiac output. The total systemic vascular resistance (SVR) decreased by 41 +/- 5%, whereas the pulmonary vascular resistance (PVR) increased by 25 +/- 6% during acute hypoxia. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg) attenuated systemic vasodilatation and enhanced pulmonary vasoconstriction. In rats with prior exposure to chronic hypobaric hypoxia, the baseline values of mean pulmonary and systemic arterial pressure were significantly higher than those in the normoxic group. Chronic hypoxia caused right ventricular hypertrophy, as evidenced by a greater weight ratio of the right ventricle to the left ventricle and the interventricular septum compared to the normoxic group (46 +/- 4 vs. 28 +/- 3%). In rats which were previously exposed to chronic hypoxia (half room air for 15 days), acute hypoxia reduced SVR by 14 +/- 6% and increased PVR by 17 +/- 4%. Pretreatment with L-NAME further inhibited the systemic vasodilatation effect of acute hypoxia, but did not enhance pulmonary vasoconstriction. Our results suggest that the release of NO counteracts pulmonary vasoconstriction but lowers systemic vasodilatation on exposure to acute hypoxia, and these responses are attenuated following adaptation to chronic hypoxia.
authors.affiliation: Department of Critical Care Medicine, Tri-Service General Hospital, Taipei, Taiwan, ROC. kun@ndmctsgh.edu.tw
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.forename: Chin-Pyng
authors.initials: CP
authors.lastname: Wu
authors.forename: Bor-Hwang
authors.initials: BH
authors.lastname: Kang
authors.forename: Yu-Chong
authors.initials: YC
authors.lastname: Lin
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D007022:Hypotension / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester