Effects of pimobendan, a cardiotonic and vasodilating agent with phosphodiesterase inhibiting properties, on isolated arteries and veins of rats.
Effects of pimobendan (PBD) were investigated on isolated rat blood vessels. PBD dose-dependently relaxed aortic, femoral arterial and mesenteric venous preparations precontracted with KCl and reduced the amplitude of spontaneous contractions of portal venous preparations; the sensitivity to PBD was femoral greater than portal greater than mesenteric greater than aorta. Relaxation response of the femoral artery to PBD was not changed by propranolol and aminophylline. Glyceryl trinitrate (GTN), isoproterenol (ISO), forskolin and adenosine also elicited dose-dependent relaxations of femoral arteries; the rank order of potency (mean negative log EC50 value) was GTN greater than ISO greater than PBD = forskolin greater than adenosine. The relaxation responses to PBD and isobutyl methylaxanthine (IBMX) were not attenuated with removal of endothelial cells. In the femoral artery, methylene blue diminished GTN-induced relaxation but not PBD-induced relaxation. PBD and IBMX increased the relaxation responses of the artery to cyclic AMP-forming drugs (ISO, forskolin and adenosine) but not a cyclic GMP-forming drug (GTN). PBD and IBMX increased the relaxation response of mesenteric veins to ISO. The drugs noncompetitively inhibited arterial contractions accompanied by voltage-dependent and alpha-adrenoceptor-operated Ca2+ influxes. In the absence of extracellular Ca2+, PBD and IBMX reduced contractile responses of arteries to norepinephrine but not caffeine. The present results suggested that PBD relaxed the blood vessels, at least in part, through an intracellular accumulation of cyclic AMP.
Department of Pharmacology, Nagoya City University Medical School, Japan.
S
S
Fujimoto
T
T
Matsuda
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D014665:Vasodilator Agents; D005576:Colforsin; D000628:Aminophylline; C041648:pimobendan; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine