作者: Mitchell I. Steinberg , Phil Ertel , Jeffrey K. Smallwood , Virginia Wyss , Karen Zimmerman
DOI: 10.1097/00005344-198812002-00007
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摘要: Pinacidil may represent an example of a new class vasodilators that act by increasing membrane permeability to potassium ions. In the present study, cardiac electrophysiological and venorelaxant effects series pinacidil analogs in canine tissues vitro were examined. Piacidil (3 x 10(-5) M) markedly reduced action potential duration Purkinje fibers (82 +/- 3% decrease) ventricular muscle (54 2% without significantly affecting maximal upstroke velocity or conduction time. The EC50 for reduction fiber was 2.6 0.5 microM. also decreased barium-induced automaticity fibers; concentration rate firing 50% identical decreasing duration. some preparations, high concentrations (greater than equal 3 associated with appearance spontaneous potentials closely coupled preceding driven potential. relaxing phenylephrine-contracted cephalic veins 0.43 0.09 microM, isolated cat papillary muscle, had direct negative inotropic effect 4.1 0.7 Thus, 6 10 times more potent shortening contractility. There excellent correlation (r = 0.933, p 0.002) between decreases venorelaxation all analogs, as well BRL 34915 nicorandil, two purported channel openers. Significant correlations obtained reductions series. (10(-5) inhibited venoconstrictor responses selective alpha 2 agonist, B-HT 920, greater extent 1 methoxamine. Since good exists among compounds studied reducing duration, vascular tissue, contractility, it is concluded nicorandil affect similar mechanisms, possibly increases ion permeability, although other mechanisms play role.