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The Effect of Inhaled L‐arginine on Pulmonary Hypertension Induced by Hypoxia or Intravenous Arginase Infusion
Author(s) -
Vrancken K,
Power G G,
Job L,
Wilson S M,
Blood A B
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1002.10
Subject(s) - arginase , inhalation , hypoxia (environmental) , medicine , pulmonary hypertension , saline , nitric oxide , vascular resistance , anesthesia , hypoxic pulmonary vasoconstriction , arginine , endocrinology , hemodynamics , chemistry , oxygen , biochemistry , organic chemistry , amino acid
Background Failure of the pulmonary vasculature to produce nitric oxide (NO) results in elevated pulmonary vascular resistance (PVR). L‐arginine (L‐arg) deficiency may be etiologic in some types of pulmonary hypertension (PH). Objective To test the hypotheses that inhalation of L‐arg will attenuate PH induced by hypoxia or an intravenous infusion of arginase, and that depletion of plasma L‐arg will result in elevated PVR. Design/Methods 15 healthy newborn lambs 5‐10 days of age were anesthetized and maintained on a mechanical ventilator. Pulmonary arterial (PAP) and venous pressure and cardiac output were measured. 12 lambs were exposed to 6 sequential 10‐min periods of hypoxia. Inhaled L‐arg or saline was administered prior to the 4 th hypoxic episode. In an additional 3 sheep, intravenous arginase was infused. Inhaled L‐arg was then administered for 15 min. Results Repeated episodes of hypoxia resulted in a rapid selective onset of PH. L‐arg inhalation caused no significant difference in PAP, PVR, or exhaled NO as compared to saline controls. Arginase resulted in a rapid significant increase in PAP (p <0.001), and in PVR (p < 0.05). PAP and PVR both decreased gradually during L‐arg inhalation, returning to control values by the end of the arginase infusion. Conclusions Plasma L‐arg is vital for the maintenance of low PVR. Preliminary results indicate that L‐arg inhalation may be effective in decreasing PH caused by L‐arg deficiency.