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 remodeling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeling decreases the vasodilatory effectiveness of iNO due to a thickened diffu...

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Bibliographic Details
Published in:	Respiration physiology Vol. 114; no. 2; pp. 161 - 173
Main Authors:	Resta, ThomasC, Sanders, ThomasC, Eichinger, MarkR, Crowley, MarkR, Walker, BenjimenR
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier B.V 01-11-1998 Amsterdam Elsevier
Subjects:	15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology Administration, Inhalation Animals Biological and medical sciences Blood flow, pulmonary, NO Blood Vessels - pathology Blood vessels and receptors Body Fluids - metabolism Chronic Disease Erythrocytes - physiology Fundamental and applied biological sciences. Psychology Hypertension, pulmonary, NO Hypoxia - pathology Hypoxia - physiopathology Hypoxia, chronic, effect of NO In Vitro Techniques Lung - metabolism Male Mammals, rat Mediators, NO Nitric Oxide - administration & dosage Nitric Oxide - pharmacology Perfusion Pulmonary Circulation - drug effects Rats Rats, Sprague-Dawley Vascular Resistance - drug effects Vasoconstrictor Agents - pharmacology Vasodilator Agents - administration & dosage Vasodilator Agents - pharmacology Vertebrates: cardiovascular system Hypertension, pulmonary, NO Blood flow, pulmonary, NO Mediators, NO Hypoxia, chronic, effect of NO Mammals, rat Oxygen Rat Respiratory disease Lung Rodentia Cardiovascular disease Permeability Respiratory system Pulmonary hypertension Vasodilation Vascular remodeling Vasomotricity Vertebrata Mammalia Nitric oxide Blood vessel Hypoxia Blood pressure Hemodynamics Circulatory system
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Summary:	Inhaled nitric oxide (iNO) is being used to treat pulmonary hypertension in a variety of chronic lung diseases associated with pulmonary vascular remodeling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeling decreases the vasodilatory effectiveness of iNO due to a thickened diffusional barrier. We therefore examined segmental vasodilatory responses to iNO 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 fluid flux and vascular wall thickness in lungs from each group to provide an index of vascular permeability and vascular remodeling, respectively. CH was associated with decreased venous, but not arterial, responsiveness to iNO in 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 largely dependent upon transport of NO from an upstream site. In contrast, RBC had no effect on arterial dilation in control lungs, but attenuated arterial dilation to iNO in lungs from CH rats. Finally, fluid flux and arterial wall thickness were greater in lungs from CH rats. We conclude that arterial remodeling associated with CH may limit venous dilation to iNO. Furthermore, the decreased arterial responsiveness to iNO following CH is consistent with extravasation of hemoglobin within the arterial vasculature.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0034-5687
DOI:	10.1016/S0034-5687(98)00086-3