Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats.
Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.
Lai
Y L
YL
Pharmacology and Experimental Therapeutics Division, College of Pharmacy, University of Kentucky, Lexington 40536.
Olson
J W
JW
Gillespie
M N
MN
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects / Q000502:physiology; D008297:Male; D016686:Monocrotaline; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011763:Pyrrolizidine Alkaloids; D016686:Monocrotaline