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(Circulation. 1999;100:1316-1321.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Hemodynamic Effects of Basal and Stimulated Release of Endogenous Nitric Oxide in Isolated Human Lungs

George Cremona, MD, PhD; Timothy W. Higenbottam, MD, FRCP; Edward A. Bower, DVM, PhD¹; Alison M. Wood, PhD; Susan Stewart, FRCPath

From the Pulmonary Division, "Salvatore Maugeri" Foundation IRCCS, Medical Centre, Veruno, Italy (G.C.); the Section of Respiratory Medicine, University Division of Clinical Sciences, The Medical School, University of Sheffield (UK) (T.W.H.); Physiological Laboratory, University of Cambridge (UK) (E.A.B.); the Department of Surgery, Royal Infirmary, Glasgow, UK (A.M.W.); and the Department of Histopathology, Papworth Hospital, Cambridge, UK (S.S.).

Correspondence to Prof Tim Higenbottam, Department of Respiratory Medicine, University Division of Clinical Sciences, The Medical School, Floor F, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK.

Background—We compared the hemodynamic responses to inhibition or stimulation of endothelial nitric oxide (NO) release of isolated explanted lungs from transplantation recipients with pulmonary hypertension and in normotensive unallocated donor lungs.

Methods and Results—Lungs from 10 patients with severe pulmonary hypertension (SPH) and from 16 patients with severe chronic obstructive lung disease (COLD) were studied. Fourteen normotensive lungs were studied as controls. The lungs were perfused at a constant flow. In protocol 1 N^G-nitro-L-arginine methyl ester caused a similar rise in baseline pulmonary artery pressure (PAP) that was similar in SPH (+17.1±4.2 mm Hg; n=5), COLD (+15.5±4.8 mm Hg; n=8), and control lungs (+14.5±1.5 mm Hg; n=7). Arterial occlusion demonstrated that most of the changes with N^G-nitro-L-arginine methyl ester were precapillary. The response to sodium nitroprusside (10^-8 to 10^-4 mol/L) was similar in all groups. In protocol 2, the lungs were preconstricted, and acetylcholine (10^-9 to 10^-5 mol/L) caused a lesser fall in PAP in both COLD and SPH lungs compared with control (-41.9±8.6%, -55.7±7.6%, and -73.2±2.5%, respectively; P<0.05), whereas sodium nitroprusside (10^-5 mol/L) decreased PAP to initial levels in all lungs.

Conclusions—Stimulated release of NO is impaired in arteries of lungs with plexogenic or hypoxemic pulmonary hypertension. In contrast, basal release of NO appears to be maintained.

Key Words: endothelium-derived factors • lung • endothelium • hypertension • vasculature • hypoxia

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