Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male rats were exposed to freshly generated cigarette smoke once daily for various lengths of time. Inhalation of smoke was verified by elevated levels of carboxyhemoglobin. Metabolism of arachidonate in the cardiovascular system to thromboxane and prostacyclin through the cyclooxygenase pathway and their further metabolism to 15-keto-derivatives, and to 12-hydroxyeicosatetraenoic acid (12-HETE) through lipoxygenase pathway was investigated. Synthesis of thromboxane and prostacyclin in platelets and aortas respectively was not changed within 8 weeks of smoke exposure. However, formation of 12-HETE in platelets was significantly increased after 4 weeks of smoke exposure. Catabolism of thromboxane and prostacyclin as determined by NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase activity was greatly decreased in lung but not in kidney and stomach following 4 weeks of smoke exposure. Increased 12-lipoxygenase activity in platelets may lead to stimulation of migration and proliferation of smooth muscle cells and to increased synthesis of leukotrienes in neutrophils. Decreased pulmonary prostaglandin catabolic activity may result in increase in circulating thromboxane/prostacyclin ratio and subsequently alteration of vascular homeostasis. The consequence of these biochemical changes may contribute to the development of atherosclerosis, thromboembolism and emphysema commonly found in smokers.
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PMID:Alterations of arachidonate metabolism in cardiovascular system by cigarette smoking. 212 9

Male rats were exposed to freshly generated cigarette smoke once daily for 4 to 8 weeks. Inhalation of smoke was verified by elevated level of carboxyhemoglobin. Arachidonate metabolism through lipoxygenase and cyclooxygenase pathways in platelets was determined. Cigarette smoking increased 12-lipoxygenase activity significantly without affecting the cyclooxygenase pathway. In view of platelet-leukocyte interactions and potent chemotactic activity of 12-HETE for aortic smooth muscle cell migration, increased 12-lipoxygenase activity may predispose individuals to atherosclerosis, thromboembolism and emphysema commonly found in smokers.
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PMID:Cigarette smoking stimulates lipoxygenase but not cyclooxygenase pathway in platelets. 641 70

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.
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PMID:Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism. 1100 74