Antibody-mediated neutrophil depletion preserves pulmonary vasomotor function.
Neutrophil depletion is commonly used to examine the role of neutrophils in lung injury. However, the effect of neutrophil depletion per se on mechanisms of pulmonary vascular smooth muscle relaxation is unknown. The purpose of this study was to examine the effect of neutropenia on the following mechanisms of cGMP-mediated pulmonary vasorelaxation: (1) receptor-dependent endothelium-dependent relaxation (response to acetylcholine (ACh)), (2) receptor-independent endothelium-dependent relaxation (response to the calcium ionophore A23187), and (3) endothelium-independent relaxation (response to sodium nitroprusside (SNP)). Neutropenia (<75 neutrophils/mu l) was induced with anti-neutrophil antibody serum 24 hr prior to lung harvest in five rats. Saline-injected rats were controls (n = 5). Dose-response curves to ACh, A23187, and SNP were generated in isolated pulmonary artery rings preconstricted with phenylepherine. Statistical comparison was performed using one-way ANOVA with post-hoc Bonferroni-Dunn, and P < 0.05 was accepted as significant. Relaxation to ACh, A23187, and SNP was complete in both control and neutropenic rats. Thus, antibody-mediated depletion does not impair endothelial-dependent or -independent cGMP-mediated pulmonary vasorelaxation.
Sheridan
B C
BC
Department of Surgery, University of Colorado, Denver 80262, USA.
McIntyre
R C
RC
Meldrum
D R
DR
Cleveland
J C
JC
Agrafojo
J
J
Eisenach
J H
JH
Harken
A H
AH
Fullerton
D A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D007106:Immune Sera; D008168:Lung / Q000098:blood supply*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009503:Neutropenia; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000502:physiology*
D007106:Immune Sera; D009599:Nitroprusside; D000001:Calcimycin; D006152:Cyclic GMP; D000109:Acetylcholine