ABSTRACT
Treatment of bovine pulmonary artery smooth muscle mitochondria with H2O2 stimulated oxidation of GSH and NAD(P)H along with an increase in Ca2+ release. Addition of oxaloacetate to mitochondrial suspension stimulated Ca2+ release and oxidation of NAD(P)H while GSH level remained unchanged. Subsequently, addition of beta-hydroxybutyrate which reduced mitochondrial pyridine nucleotides caused reuptake of the released Ca2+ without causing appreciable alteration of GSH level. Treatment of the mitochondria with 1,3-bis(2-dichloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase, significantly decreased GSH level without producing discernible change in Ca2+ release and NAD(P)H oxidation.
Subject(s)
Animals , Calcium/metabolism , Carmustine/pharmacology , Cattle , Electron Transport Complex IV/metabolism , Glutathione/metabolism , Hydrogen Peroxide/pharmacology , Kinetics , Mitochondria/drug effects , Muscle, Smooth, Vascular/metabolism , NAD/metabolism , NADP/metabolism , Oxaloacetates/pharmacology , Oxaloacetates , Oxidation-Reduction , Pulmonary Artery/metabolismABSTRACT
The role of hydroxyl radical (OH.) in H2O2-mediated stimulation of lipid peroxidation in microsomes of bovine pulmonary arterial smooth muscle tissue and the protective effects of DIDS, the anion channel blocker have been studied. Treatment of microsomes with H2O2 (1 mM) stimulate iron release, OH. production and lipid peroxidation. Pretreatment with DFO (an iron chelator) or DMTU (a hydroxyl radical scavenger) prevents OH. production and thereby reduces lipid peroxidation without any appreciable reduction of iron release. Simultaneous treatment of either DFO or DMTU with H2O2 significantly reduces lipid peroxidation and prevents OH. production without any significant reduction of iron release. However, addition of DFO or DMTU 2 min after treatment of the microsome with H2O2 does not produce any significant reduction of lipid peroxidation, OH production and iron release. Pretreatment of microsomes with DIDS markedly reduces the stimulation of lipid peroxidation without appreciably altering the increase in OH. production and iron release caused by H2O2.
Subject(s)
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Animals , Cattle , Deferoxamine/pharmacology , Free Radical Scavengers/pharmacology , Hydrogen Peroxide/pharmacology , Hydroxyl Radical/metabolism , Ion Channels/antagonists & inhibitors , Lipid Peroxidation/drug effects , Microsomes/drug effects , Muscle, Smooth, Vascular/metabolism , Pulmonary Artery , Thiourea/analogs & derivativesABSTRACT
Substance P (SP) injection in the plantar region of rat hind paw caused a dose related inflammation, which reached a peak within 10 min of injection and declined after 60 min. Low doses (0.25-0.063 mg/kg) of SP-antagonists like (D-Pro2, D-Trp7,9)-SP and (D-Pro2, D-Phe7, D-Trp9)-SP pretreatment significantly inhibited the SP induced paw oedema, while higher doses (0.5-1 mg/kg) showed agonistic effects. Pretreatment with diphenhydramine alone or along with low doses of SP-antagonists was highly significant in blocking this inflammation, the latter combination being more effective than the former. Pretreatment with acute capsaicin produced a synergestic effect on SP induced paw oedema, while pretreatment with chronic capsaicin significantly inhibited this SP induced paw oedema. The results indicate involvement of histamine and possible therapeutic importance of capsaicin in SP mediated inflammatory type of responses.