AJP - Heart and Circulatory Physiology, Vol 243, Issue 4 505-H511, Copyright © 1982 by American Physiological Society
alpha-Naphthylthiourea produces dose-dependent lung vascular injury in sheep
A. M. Havill, M. H. Gee, J. D. Washburne, A. Premkumar, R. Ottaviano, J. T. Flynn and J. A. Spath Jr
We tested the effects of alpha-naphthylthiourea (ANTU) on lung fluid
balance and prostanoid concentrations in anesthetized sheep acutely
prepared for collection of pulmonary lymph. Sheep were given 20, 50, 75, or
100 mg/kg ANTU or the vehicle dimethylsulfoxide (DMSO) intravenously. The
first phase of the response consisted of transient increases in pulmonary
artery pressure and plasma and lymph thromboxane B2 concentrations. Lymph
flow increased with no change in the lymph-to-plasma protein concentration
ratio (L/P). These changes occurred in sheep given DMSO alone or DMSO with
ANTU; they were not dependent on the dose of ANTU given. Two to 4 h after
drug administration, pulmonary artery pressure and thromboxane
concentrations were normal or near normal. Lymph flow rate reached
steady-state levels averaging 1.5 (DMSO alone) to 5.3 (100 mg/kg ANTU)
times base line with L/P ratios unchanged from base line. ANTU/DMSO
produces transient, severe pulmonary hypertension that may be prostaglandin
mediated. The sustained response consists of increased flow rate of
protein-rich lymph.
