Segmental vasodilatory effectiveness of inhaled NO in lungs from chronically hypoxic rats

Inhaled nitric oxide (iNO) is being used to treat pulmonary hypertension in a variety of chronic lung diseases associated with pulmonary vascular remo deling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeli ng decreases the vasodilatory effectiveness of iNO due to a thickened diffu sional barrier. We therefore examined segmental vasodilatory responses to i NO in U-46619-constricted lungs isolated from control and CH (4 weeks at 0. 5 atm) rats using double occlusion technique. We further measured lung flui d Bur and vascular wall thickness in lungs from each group to provide an in dex of vascular permeability and vascular remodeling, respectively. CH was associated with decreased venous, but not arterial, responsiveness to iNO i n saline-perfused lungs. In addition, the presence of red blood cells (RBC) within the perfusate greatly reduced venodilation in both groups of lungs, indicating that venous responsiveness to iNO in saline-perfused lungs is l argely dependent upon transport of NO from an upstream site. In contrast, W BC had no effect on arterial dilation in control lungs, but attenuated arte rial dilation to iNO in lungs from CH rats. Finally, fluid flux and arteria l wall thickness were greater in lungs from CH rats. We conclude that arter ial remodeling associated with CH may limit venous dilation to iNO. Further more, the decreased arterial responsiveness to iNO following CH is consiste nt with extravasation of hemoglobin within the arterial vasculature. (C) 19 98 Elsevier Science B.V. All rights reserved.