title: The effects of nitric oxide synthase--versus lipoxygenase inhibition on coronary flow and nitrite outflow in isolated rat heart.
abstract: The aim of this study was to assess the changes of coronary flow (CF) and nitrite outflow under inhibition of nitric oxide synthase (NOS) by Nomega-nitro-L-arginine monomethyl ester (L-NAME) or lipoxygenase (LOX) induced by nordihydroguaiaretic acid (NDGA) in isolated rat heart. The hearts of male Wistar albino rats (n=18, age 8 weeks, body mass 180-200 g) were retrograde perfused according to the Langendorff's technique at gradually increased constant coronary perfusion pressure (CPP) conditions (40-120 cm H2O) which induced flow-dependent nitric oxide (NO) release (nitrite outflow). The experiments were performed during control conditions, in the presence of NO synthesis inhibitor L-NAME (30 micromol/l) or nonspecific LOX inhibitor (NDGA, 0.1 mmol/l) which were administered separately or in combination. CF varied in autoregulatory range from 4.12+/-0.26 ml/min/g wt at 50 cm H2O to 5.22+/-0.26 ml/min/g wt at 90 cm H2O. In autoregulatory range, nitrite outflow varied from 2.05+/-0.17 nmol/min/g wt at 50 cm H2O to 2.52+/-0.21 nmol/min/g wt at 90 cm H2O and was strictly parallel with CPP/CF curve. The autoregulatory range of CF was significantly extended (40-100 cm H2O, 2.22+/-0.12 ml/min/g wt and 2.90+/-0.25 ml/min/g wt, respectively) under the influence of L-NAME. Hemodynamic effects were accompanied by significant decrease in nitrite outflow after L-NAME administration (0.56+/-0.11 nmol/min/g wt at 40 cm H2O to 1.45+/-0.14 nmol/min/g wt at 100 cm H2O). NDGA affected CF in the range of CPP 40-70 cm H2O only (from 42% at 50 cm H2O to 12% at 90 cm H2O, respectively) with no significant changes in nitrite outflow. When L-NAME was applied in combination with NDGA vs. NDGA only, CF was significantly reduced (from 34% at 50 cm H2O to 50% at 90 cm H2O, respectively) with parallel changes in nitrite outflow (from 40% at 50 cm H2O to 51% at 90 cm H2O, respectively). The results showed that CF and nitrite outflow could be decreased under L-NAME administration. Nonselective LOX inhibitor (NDGA) decreased control values of CF only at lower values of CPP but did not change nitrite outflow indicating antioxidant properties of NDGA. In addition, L-NAME decreased the effects induced by NDGA on CF and nitrite outflow indicating the role of NO.
authors.affiliation: Department of Physiology, Faculty of Medicine, Svetozara Markovića 69, P.O.Box 124, 34000 Kragujevac, Serbia and Montenegro. drvladakg@yahoo.com
authors.forename: V Lj
authors.initials: VLj
authors.lastname: Jakovljevic
authors.forename: D M
authors.initials: DM
authors.lastname: Djuric
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016859:Lipoxygenase Inhibitors; D009573:Nitrites; D009637:Masoprocol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester