Mathew, Rajamma, Elizabeth S. Gloster, T. Sundararajan, Carl I. Thompson, Guillermo A. Zeballos, and Michael H. Gewitz. Role of inhibition of nitric oxide production in monocrotaline-induced pulmonary hypertension. J. Appl. Physiol. 82(5): 1493–1498, 1997.—Monocrotaline (MCT)-induced pulmonary hypertension (PH) is associated with impaired endothelium-dependent nitric oxide (NO)-mediated relaxation. To examine the role of NO in PH, Sprague-Dawley rats were given a single subcutaneous injection of normal saline [control (C)], 80 mg/kg MCT, or the same dose of MCT and a continuous subcutaneous infusion of 2 mg ⋅ kg−1 ⋅ day−1of molsidomine, a NO prodrug (MCT+MD). Two weeks later, plasma[Formula: see text] levels, pulmonary arterial pressure (Ppa), ratio of right-to-left ventricular weights (RV/LV) to assess right ventricular hypertrophy, and pulmonary histology were evaluated. The plasma [Formula: see text] level in the MCT group was reduced to 9.2 ± 1.5 μM ( n = 12) vs. C level of 17.7 ± 1.8 μM ( n = 8; P < 0.02). In the MCT+MD group, plasma [Formula: see text] level was 12.3 ± 2.0 μM ( n = 8). Ppa and RV/LV in the MCT group were increased compared with C [Ppa, 34 ± 3.4 mmHg ( n = 6) vs. 19 ± 0.8 mmHg ( n = 8) and 0.41 ± 0.01 ( n = 9) vs. 0.25 ± 0.008 ( n = 8), respectively; P < 0.001]. In the MCT+MD group, Ppa and RV/LV were not different when compared with C [19 ± 0.5 mmHg ( n = 5) and 0.27 ± 0.01 ( n = 9), respectively; P < 0.001 vs. MCT]. Medial wall thickness of lung vessels in the MCT group was increased compared with C [31 ± 1.5% ( n = 9) vs. 13 ± 0.66% ( n = 9); P < 0.001], and MD partially prevented MCT-induced pulmonary vascular remodeling [22 ± 1.2% ( n = 11); P < 0.001 vs. MCT and C]. These results indicate that a defect in the availability of bioactive NO may play an important role in the pathogenesis of MCT-induced PH.
Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction.
