Mechanistic imbalance of pulmonary vasomotor control in progressive lung injury.
BACKGROUND
Pulmonary hypertension is the major hemodynamic feature of progressive lung injury. We hypothesized that the mechanisms of pulmonary vasorelaxation become progressively impaired in progressive lung injury. The purpose of this study was to examine the following mechanisms of pulmonary vasorelaxation in a rat model of monocrotaline-induced progressive lung injury: endothelial-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), endothelial-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol), and hypoxic pulmonary vasoconstriction.


METHODS
Rats were studied 2, 7, and 14 days after monocrotaline injection (100 mg/kg intraperitoneally). Pulmonary vasomotor control mechanisms were studied in isolated pulmonary artery rings. Controls were studied 14 days after saline injection. Statistical analysis was by ANOVA; p < 0.05 was considered significant.


RESULTS
A progressive impairment of pulmonary vasorelaxation was observed. By 14 days after monocrotaline injection acetylcholine produced only 25% +/- 5% relaxation versus 95% +/- 5% in controls (p < 0.05), nitroprusside produced 46% +/- 5% relaxation versus 100% in controls (p < 0.05), and isoproterenol produced only 18% +/- 5% relaxation versus 94% +/- 4% in controls (p < 0.05). At the same time hypoxic pulmonary vasoconstriction became progressively exaggerated.


CONCLUSIONS
Progressive dysfunction of pulmonary vasomotor control may contribute to the pulmonary hypertension seen in progressive lung injury.
Fullerton
D A
DA
Department of Surgery, University of Colorado, Denver, USA.
Hahn
A R
AR
McIntyre
R C
RC
D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D014666:Vasomotor System
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D006152:Cyclic GMP