title: Vasorelaxant effect of olprinone, an inhibitor of phosphodiesterase 3, on mesenteric small artery and vein of rabbits.
abstract: The effects of olprinone, a cardiotonic agent that inhibits cyclic GMP (cGMP)-inhibited phosphodiesterase, was studied on isolated rabbit mesenteric small artery and vein. In the presence of indomethacin and propranolol, olprinone at concentrations of 10 nM to 10 microM and 1 microM to 100 microM relaxed norepinephrine-stimulated mesenteric artery and vein in a concentration-dependent manner, respectively. The relaxation was not endothelium-dependent in the artery. Removal of the endothelium, however, increased marginally the response of the vein to olprinone. Olprinone-induced relaxation was less pronounced in arteries contracted with high KCl solution + norepinephrine than in those contracted with norepinephrine alone. Nicardipine inhibited this attenuating effect of high KCl solution on the olprinone-induced relaxation. Olprinone (1 microM) enhanced the relaxation of artery and vein in response to a cAMP-increasing agent, 6-(3-dimethylaminopropionyl) forskolin (NKH477), but not to a cGMP- increasing agent, glyceryl trinitrate. Norepinephrine (10 microM) and caffeine (5 mM) elicited a transient, phasic contraction of the artery in Ca2+-free solution. Both olprinone and NKH477 attenuated more potently the norepinephrine-induced contraction than the caffeine-induced contraction. When norepinephrine (10 microM) and caffeine (5 mM) were successively applied in Ca2+-free solution, the contractile effect of caffeine was diminished compared to that in artery which had not been pretreated with norepinephrine. When the contraction in response to norepinephrine was partially attenuated by 1 microM olprinone, the following contraction evoked by caffeine was enlarged. It is concluded that olprinone relaxes the small artery more strongly than the vein via its direct action on smooth muscles. It is suggested that olprinone attenuates norepinephrine-induced contraction through inhibition of receptor-operated transmembrane Ca2+ influx and Ca2+ release from intracellular storage sites.
authors.affiliation: Department of Pharmacology, Nagoya City University Medical School, Nagoya, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: A
authors.initials: A
authors.lastname: Hiramoto
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: H
authors.initials: H
authors.lastname: Shiokawa
authors.forename: T
authors.initials: T
authors.lastname: Itoh
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D014665:Vasodilator Agents; D005576:Colforsin; D002110:Caffeine; C059498:olprinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005996:Nitroglycerin; D002118:Calcium