Effects of phosphodiesterase V inhibition on nitric oxide-mediated relaxation responses in guinea pig trachea.
In the present study, we aimed to evaluate the effects of PDE V inhibition on NO-mediated relaxation responses in isolated guinea pig trachea. Under the NANC conditions, tracheal preparations were contracted with histamine (100 microm/l). When contraction had reached a plateau, relaxation responses to electrical field stimulation (EFS, 60 V, 0.5 ms, 5-10 Hz) were determined before and after incubation of the tracheal ring with L-NAME (1 mmol/l), a NO synthase inhibitor. L-NAME significantly inhibited the relaxation responses and this inhibitory effect was reversed by L-arginine (1 mmol/l), a precursor of NO, but was not affected by D-arginine. In addition, cumulative application of the NO donors, 3-morpholino-sydnonimine (SIN-1) and sodium nitroprusside (SNP), caused concentration-dependent relaxation of tissues precontracted with histamine. The selective PDE type V inhibitor zaprinast at EC50 concentration (30 micromol/l) significantly potentiated EFS-induced NANC relaxations and relaxant responses to SIN-1 and SNP. In conclusion, these data support the hypothesis that NO is a mediator of NANC relaxations of guinea pig tracheal rings and PDE V inhibition potentiates NO-mediated relaxation.
Tuncel
Başak I
BI
Department of Pharmacology, Akdeniz University Faculty of Medicine, Arapsuyu, Antalya, Turkey. basaktuncel@akdeniz.edu.tr
Sadan
Gülay
G
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004558:Electric Stimulation / Q000379:methods; D004566:Electrodes; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007536:Isomerism; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000187:drug effects* / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D006632:Histamine; D001120:Arginine; D008981:Molsidomine; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C011145:zaprinast; D019331:NG-Nitroarginine Methyl Ester