4-Aminopyridine induces positive lusitropic effects and prevents the negative inotropic action of phenylephrine in the rat cardiac tissue subjected to ischaemia.
The effects of 4-aminopyridine (4-AP) at concentration of 1 mM on the contractility of rat isolated papillary muscle subjected to simulated ischaemia has been evaluated. Additionally, the effects of 4-AP on the phenylephrine inotropic action (a selective agonist of alpha1-adrenergic receptor) on rat isolated cardiac tissue underwent simulated ischaemia and reperfusion was studied. Experiments were performed on rat isolated papillary muscles obtained from left ventricle. The following parameters have been measured: force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and the ratio between time to peak contraction (ttp) and relaxation time at the level of 10% of total contraction amplitude (tt10) as an index of lusitropic effects. Simulated ischaemia lasting 45 min was induced by replacement of standard normoxic solution by no-substrat one gassing with 95% N2/5%CO2. Although 4-AP exerted a slight, but significant positive inotropic action itself, pretreatment with 1 mM of this compound significantly depressed a recovery of Fc and +dF/dt, but improves recovery of -dF/dt in the rat papillary muscle during reperfusion as compared with control group of preparations. Moreover, the paradoxical negative inotropic action of phenylephrine observed in rat stunned papillary muscle was prevented in preparations previously treated by 4-AP. These findings suggest that an inhibition of outward K+ current (probably transient outward and rapid component of delayed rectifying currents at 1 mM of 4-AP) aggravates ischaemia-induced failure in contractility but prevents changes in alpha1-adrenergic receptor signaling pathway occuring during ischaemia.
Kocić
I
I
Department of Pharmacology, Medical University of Gdańsk, Poland.
Dworakowska
D
D
Dworakowski
R
R
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D010210:Papillary Muscles / Q000187:drug effects* / Q000503:physiopathology*; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D010656:Phenylephrine; D015761:4-Aminopyridine