Journal of Applied Physiology, Vol 70, Issue 2 561-566, Copyright © 1991 by American Physiological Society

ARTICLES

Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats

Y. L. Lai, J. W. Olson and M. N. Gillespie
Pharmacology and Experimental Therapeutics Division, College of Pharmacy, University of Kentucky, Lexington 40536.

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.

This article has been cited by other articles:

				M. Clozel, P. Hess, M. Rey, M. Iglarz, C. Binkert, and C. Qiu Bosentan, sildenafil, and their combination in the monocrotaline model of pulmonary hypertension in rats. Experimental Biology and Medicine, June 1, 2006; 231(6): 967 - 973. [Abstract] [Full Text] [PDF]

				F J Meyer, R Ewert, M M Hoeper, H Olschewski, J Behr, J Winkler, H Wilkens, C Breuer, W Kubler, and M M Borst Peripheral airway obstruction in primary pulmonary hypertension Thorax, June 1, 2002; 57(6): 473 - 476. [Abstract] [Full Text] [PDF]

				P. H. M. Hoet and B. Nemery Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L417 - L433. [Abstract] [Full Text] [PDF]

				G. L. Colice, N. Hill, Y.-J. Lee, H. Du, J. Klinger, J. C. Leiter, and L.-C. Ou Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness J Appl Physiol, July 1, 1997; 83(1): 25 - 31. [Abstract] [Full Text] [PDF]

				Y. L. Lai and K.-R. Zhou Eglin-c prevents monocrotaline-induced ventilatory dysfunction J Appl Physiol, January 1, 1997; 82(1): 324 - 328. [Abstract] [Full Text] [PDF]