Effects of [Na+] and [Ca2+] on the responses to milrinone in rat cardiac preparations.
In the present investigation we have studied the influence of changing the [Ca2+] and [Na+] on the cardiac responses to milrinone in various preparations of rat heart. Milrinone (5 X 10(-5) to 8 X 10(-4) M) produced a dose-dependent positive chronotropic effect on right atrium and a positive inotropic effect on left atrium and papillary muscle of the rat. A decrease in [Ca2+] (from 2.2 to 1.1 mM) or an increase in [Na+] (from 120 to 60 mM) increased the milrinone-induced inotropic effect in left atrium and papillary muscle. However, in right atrium the chronotropic effect of milrinone was significantly decreased under these conditions. Opposite changes to milrinone-induced responses were observed when [Ca2+] was increased (to 3.3 mM) or when the [Na+] was decreased to 60 mM. Nifedipine (3 X 10(-3) M), a selective Ca2+ channel blocker, significantly inhibited the chronotropic response to milrinone in right atrium. However, the inotropic response to milrinone was found to be significantly greater in the presence of nifedipine. A veratridine-induced positive inotropic effect in the left atrium was also significantly increased in the presence of nifedipine. Tetrodotoxin (TTX, 1 X 10(-6) M), a fast sodium channel blocker, significantly reduced the inotropic response to milrinone in left atrium and papillary muscle. A milrinone-induced dose-dependent increase in the baseline tension was observed in the right atrium which was abolished in low [Ca2+] and significantly increased in high [Ca2+]. Our data suggest the possibility that milrinone increases Ca2+ influx in the right atrium to cause the chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D020105:Milrinone; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002316:Cardiotonic Agents; D011728:Pyridones; D013779:Tetrodotoxin; D014701:Veratridine; D012964:Sodium; D009543:Nifedipine; D020105:Milrinone; D002118:Calcium