title: Nitric oxide effects depend on different mechanisms in different regions of the rat heart.
abstract: The important role of nitric oxide (NO) in regulating cardiac functions has been investigated in prior research. However, NO-induced signaling mechanisms in the different regions of the heart have not been explored until now. In this study, the mechanism of NO effects on the spontaneously beating right atrium and left papillary muscle isolated from the rat heart was examined. The NO donor diethylamine NONOate (DEA/NO) (0.1-100 μM) depressed the resting and developed tensions, as well as the sinus rate, of the right atrium. The effect of DEA/NO on contractions of the right atrium was blocked by the soluble guanylate cyclase (sGC) inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one) (10 μM). The ATP-sensitive potassium channel (K(ATP)) blocker glyburide (3 μM) reversed DEA/NO-induced decreases in the resting tension. The suppressor effect of DEA/NO on the sinus rate was inhibited only by the superoxide radical scavenger superoxide dismutase (25 U/ml). Neither the cGMP-dependent protein kinase (PKG) inhibitor KT5823 (0.1 μM) nor the cAMP-dependent protein kinase (PKA) inhibitor KT5720 (1 μM) changed DEA/NO responses in the right atrium. While the resting tension of the right atrium was decreased by the NO precursor L-arginine (1-100 μM), it was increased by the nitric oxide synthase inhibitor L-NMMA (0.1-100 μM). The sinus rate was not affected by L-arginine or L-NMMA. The left papillary muscle contraction was not influenced by any of these NO-related agents. These results show that high concentration NO-induced depression of the contraction of the right atrium is due to sGC and K(ATP) channel activation, but suppression of the sinus rate depends on redox regulation. Our results may have important implications for the region-dependent functional disability of cardiac myocytes, as well as the regulation of heart performance in high NO-induced pathological conditions.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, 06100, Ankara, Turkey.
authors.forename: Kursat
authors.initials: K
authors.lastname: Derici
authors.forename: Ufuk
authors.initials: U
authors.lastname: Samsar
authors.forename: Emine
authors.initials: E
authors.lastname: Demirel-Yilmaz
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D006834:Hydrazines; D054086:KATP Channels; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase