[Effects of ATP-regulated potassium channels modulators, N-(2-pyridyl)-N'-(4-toluol) sulfonylcarbamides, on electromechanical activity in guinea pig myocardium].
The aim of the study was to investigate the effects of 2-aminopyridine (2-AP) and its new sulfonylcarbamide derivatives AP21, AP22, AP26, and AP27 (10(-(5))-10(-(3)) M) on pinacidil (5x10(-(5)) M), an activator of K(ATP) channels, induced shortening of action potential duration and reduction of contraction force in guinea pig papillary muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of papillary muscles with Tyrode solution), an average of action potential duration (APD), measured at 90% (APD(90)) and 50% (APD(50)) of repolarization, were 211.78+/-8.6 ms and 173.22+/-8.3 ms (n=18), respectively, and contraction force was 1.77+/-0.36 mN (n=18). Pinacidil markedly decreased APD(90) to 58.16+/-4.4%, APD(50) - to 52.51+/-4.85% (n=18), and contraction force - to 30.45+/-4.06% (n=18), (p<0.001) vs. control. 2-aminopyridine and its sulfonylcarbamide derivative AP22 (with 4-toluolsulfonylcarbamide fragment and methyl iodide-quaternized nitrogen of the pyridine ring) had no effect on the pinacidil-induced shortening of action potential and reduction of contraction force. 2-aminopyridine derivatives, AP21 (with 4-toluolsulfonylcarbamide fragment) and AP26 (with allyl bromide-quaternized nitrogen of the pyridine ring), showed a weak effect on pinacidil-induced shortening of action potential duration. The 2-aminopyridine derivative AP27 (with the 4-toluolsulfonylcarbamide fragment where nitrogen of the pyridine ring was quaternized by 4-nitrobenzyl bromide) had the most potent stimulatory effect on action potential duration and contraction force, which were reduced by pinacidil.
Gendviliene
Vida
V
Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 50161 Kaunas, Lithuania. membiof@kmu.lt
Zablockaite
Danguole
D
Gurskaite
Herta
H
Martisiene
Irma
I
Stankevicius
Antanas
A
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000502:physiology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D000631:Aminopyridines; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide; C032439:alpha-aminopyridine