title: Effects of rolipram on U46619-induced contraction and cyclic nucleotide content in the porcine coronary artery.
abstract: The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide content in the porcine coronary artery were investigated. Various selective PDE inhibitors, vinpocetine (type 1), erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA, type 2), milrinone (type 3), rolipram (type 4), Ro20-1724 (type 4), and zaprinast (type 5), inhibited U46619-induced contractions in a concentration-dependent manner. The rank order of potency for the porcine coronary artery was rolipram > Ro20-1724 >milrinone > vinpocetine > zaprinast > EHNA, which was different from that of both the porcine carotid artery and aorta. Rolipram inhibited the U46619-induced muscle tension with a decreased [Ca(2+)](i) level, but inhibited the high K(+)-induced contraction without a change in [Ca(2+)](i) level. Rolipram increased cAMP but not cGMP content. Iberiotoxin restored the inhibition of muscle tension and the [Ca(2+)](i) levels induced by rolipram. U46619 and caffeine induced a transient increase in the [Ca(2+)](i) levels in a Ca(2+)-free solution, but rolipram only inhibited the U46619-induced Ca(2+) transient. In conclusion, rolipram is the most potent inhibitor in the porcine coronary artery, but not in the carotid artery and aorta. Moreover it is suggested that the mechanism by which rolipram causes relaxation is due to a decrease in the [Ca(2+)](i) levels and of the Ca(2+) sensitivity of the contractile elements to cAMP.
authors.affiliation: Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Veterinary and Life Science University, Japan. t-kaneda@nvlu.ac.jp
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kaneda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kubota
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Norimoto
authors.initials: N
authors.lastname: Urakawa
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Nakajyo
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002110:Caffeine; D002118:Calcium / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D020889:Rolipram / Q000494:pharmacology*; D013552:Swine; D014662:Vasoconstrictor Agents
chemical_list: D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D002110:Caffeine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020889:Rolipram; D011188:Potassium; D002118:Calcium