title: Exhaled nitric oxide measurement to monitor pulmonary hypertension in a pneumonectomy-monocrotaline rat model.
abstract: The use of fractional exhaled nitric oxide (FeNO) has been suggested as a quantitative marker for pulmonary arterial hypertension (PAH) in humans. To further characterize FeNO in PAH we investigated this marker in a rodent model. Since there is no standardized technique for FeNO measurement in animals, we intended to reduce measuring errors and confounders of an existing published method by mathematical modification and tested its applicability in an NO-regulating therapy concept of PAH. Thirty-three male Sprague-Dawley rats underwent unilateral pneumonectomy and monocrotaline (MCT) injection and were observed for 49 days. A telemetric catheter was introduced into the left pulmonary artery to continuously record mean pulmonary arterial pressure (mPAP), and FeNO was assessed. After 35 days, animals were randomized to receive either oral l-arginine (300 mg/kg) in combination with tetrahydrobiopterin (20 mg/kg) therapy (n = 12) or vehicle (n = 11) daily over a period of 14 days. mPAP at baseline was 17.19 ± 9.62 mmHg, which increased to 53.1 ± 10.63 mmHg 28 days after monocrotaline exposure (P < 0.001). Using the modified technique, we found an inverse correlation between exhaled NO and pulmonary pressures before (r = -0.366, P = 0.043) and after MCT (r = -0.363, P = 0.038) as well as after therapy administration (r = -0.657, P = 0.02). Our modified technique proved robust in a rodent model, since valid and reproducible data were gained and showed an inverse correlation between exhaled NO and mPAP, whereas the existing method did not.
authors.affiliation: 2 med. Dept., Rudolfstiftung, Juchgasse 25, A-1030 Vienna, Austria. paul.wexberg@wienkav.at.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Strobl
authors.forename: Catharina
authors.initials: C
authors.lastname: Schreiber
authors.forename: Adelheid
authors.initials: A
authors.lastname: Panzenböck
authors.forename: Max-Paul
authors.initials: MP
authors.lastname: Winter
authors.forename: Helga
authors.initials: H
authors.lastname: Bergmeister
authors.forename: Johannes
authors.initials: J
authors.lastname: Jakowitsch
authors.forename: Julia
authors.initials: J
authors.lastname: Mascherbauer
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
authors.forename: Paul
authors.initials: P
authors.lastname: Wexberg
authors.forename: Diana
authors.initials: D
authors.lastname: Bonderman
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use; D062186:Arterial Pressure / Q000187:drug effects*; D015415:Biomarkers; D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D045853:Exhalation; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000032:analysis*; D011013:Pneumonectomy; D011651:Pulmonary Artery / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D001708:Biopterins; D009569:Nitric Oxide; D016686:Monocrotaline; D001120:Arginine; C003402:sapropterin
keywords: fractional exhaled nitric oxide; monocrotaline; noninvasive measurement; rat
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