Activated neutrophils alter contractile properties of the pulmonary artery

• Published in: American journal of respiratory cell and molecular biology Vol. 6; no. 3; p. 260
• Main Authors: Patterson, C E, Jin, N, Packer, C S, Rhoades, R A
• Format: Journal Article
• Language: English
• Published: United States 01-03-1992
• Subjects: Animals; Catalase - pharmacology; Ibuprofen - pharmacology; In Vitro Techniques; Indomethacin - pharmacology; Male; Methacrylates - pharmacology; Muscle Contraction; Muscle, Smooth, Vascular - physiology; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - drug effects; Pulmonary Artery - physiology; Rats; Rats, Inbred Strains; Superoxide Dismutase - pharmacology; Superoxides - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Thromboxane A2 - metabolism; Thromboxane-A Synthase - antagonists & inhibitors
• ISSN: 1044-1549
• DOI: 10.1165/ajrcmb/6.3.260

Activated neutrophils produce a wide array of products (free radicals, arachidonate metabolites, degradative enzymes), cause hemodynamic effects and increased permeability in isolated blood-free perfused lungs, and evoke direct injury to cultured endothelial cells. The aims of this study were to investigate the response of isolated rat pulmonary arterial rings to activated neutrophils, the role of intact endothelium in these responses, and which neutrophil products were responsible for the observed effects. Neutrophils activated with phorbol myristate acetate caused an initial increase in tension and a subsequent decreased recovery contraction to KCl. Neutrophils activated with formylmethionylleucylphenylalanine also caused an increase in tension but did not result in decreased recovery, suggesting different mechanisms for these two effects. The contractile response was dependent on endothelium, whereas the decline in recovery still occurred in the absence of endothelium. Filtrate from activated neutrophils did not cause the contractile response, but recovery was decreased. Neither addition of catalase + superoxide dismutase nor decreased superoxide release due to prior activation of neutrophils altered the initial contraction or the decline in recovery contractile ability, suggesting that oxygen free radical products were not responsible for either effect. The cyclooxygenase inhibitors (ibuprofen and indomethacin), the thromboxane A2 synthetase inhibitor (OKY-046), and pretreatment of the neutrophils with aspirin inhibited the contractile response but did not prevent the decrease in recovery. A mixture of antiproteases did not protect the arterial muscle from the decline in recovery. Although cyclooxygenase products may be involved in initiating the contraction in response to activated neutrophils, the mechanism resulting in subsequent loss of force-developing ability is unclear.