Gender differences in effects of pinacidil but not diazoxide on heart automatism in the isolated guinea pig right atria.
The aim of this paper was to investigate the effects of pinacidil and diazoxide, the activators of sarcolemmal and mitochondrial ATP-sensitive K(+) channels (K(ATP)), respectively, on heart rate and force of contraction in female and male guinea pigs. Experiments were performed on the isolated, spontaneously beating, right atria obtained from guinea pigs of both genders. First series of experiments were performed in the spring and repeated in the fall. It was found that diazoxide induced similar negative chronotropic effects in females (-logIC(50) = 4.34 +/- 0.05, E(max) = -90 +/- 6 beats min(-1)) and males (-logIC(50) = 4.42 +/- 0.1, E(max) = -91 +/- 6 beats min(-1)). Additionally, significant positive inotropic effect sensitive to 5-hydroxydecanoate was noted only in males (about 30% above control level at 300 microM). No differences in effects of diazoxide in the spring and in the fall were noted. On the other hand, pinacidil induced significant decrease in heart rate in female guinea pigs only in the fall (-logIC(50) = 4.79 +/- 0.15, E(max) = -77 +/- 9 beats min(-1)), but in males similar negative chronotropic action in the spring (-logIC(50) = 4.53 +/- 0.12, E(50) = -63 +/- 5 beats min(-1)) and in the fall (-logIC(50) = 4.75 +/- 0.2, E(max) = -59 +/- 8 beats min(-1)) was observed. Glibenclamide (10 microM), but not 5-hydroxydecanoate (300 microM) reversed negative chronotropic action of both, pinacidil and diazoxide. No significant inotropic action of pinacidil was observed.


CONCLUSIONS
Although negative chronotropic effects of pinacidil and diazoxide are related to activation of sarcolemmal K(ATP) channels, only pinacidil affects heart rate of female and male guinea pigs in a different way. This difference is probably hormone-dependent as it appeared only in the spring.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003864:Depression, Chemical; D003981:Diazoxide / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D012621:Seasons; D012737:Sex Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D000255:Adenosine Triphosphate; D003981:Diazoxide