Continuous low-dose NO inhalation does not prevent monocrotaline-induced pulmonary hypertension in rats.
We determined whether vasodilator doses of inhaled nitric oxide (NO) prevented the progression of pulmonary hypertension (PH) and vascular changes in monocrotaline-induced PH. Short-term NO inhalation in rats 3 wk after the injection of monocrotaline reduced mean pulmonary artery pressure (PAP) from 30.7 +/- 2.2 (SE) to 26.4 +/- 1.4 mmHg at 10 parts per million (ppm) and from 30.2 +/- 1.3 to 25.8 +/- 1.4 mmHg at 40 ppm. There were no differences among rats exposed to air only and rats exposed to 10 ppm of NO for 19 days after a single subcutaneous injection of monocrotaline, in mean PAP (34.3 +/- 1.9 mmHg air vs. 32.8 +/- 1.4 mmHg NO), right ventricular hypertrophy (RVH), medial wall thickness (MWT) of muscular arteries, and the percentage of muscularized arteries at alveolar wall (%AW) and duct (%AD) level. Additional groups exposed to air only and 40 ppm of NO for 19 days again showed no difference in mean PAP, RVH, MWT, and %AD, except that this dose slightly reduced %AW (60.6 +/- 3.4% air vs. 46.9 +/- 5.2% NO, P = 0.04). Urine nitrate (NO3) level was higher in rats that had inhaled NO. In contrast to chronic hypoxic PH, vasodilator doses of NO inhalation did not prevent the development of PH in this malignant form of experimental PH.
Maruyama
J
J
Department of Anesthesiology, Mie University School of Medicine, Japan.
Maruyama
K
K
Mitani
Y
Y
Kitabatake
M
M
Yamauchi
T
T
Miyasaka
K
K
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005740:Gases / Q000097:blood; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000517:prevention & control*; D008168:Lung / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D005740:Gases; D009566:Nitrates; D009569:Nitric Oxide; D012965:Sodium Chloride; D016686:Monocrotaline