Diverse inotropic effects of 5-hydroxytryptamine in heart muscles of various mammalian species.

The inotropic effects of 5-hydroxytryptamine (5-HT) on mammalian heart muscles were investigated. 5-HT (10(-8)-10(-3)M) produced increases in the contractile tension of atrial and ventricular muscles isolated from guinea pigs, Japanese monkeys, and humans, but not in rat heart preparations. The maximum percent increase of contraction was largest in guinea pig ventricular muscles (142.0 percent), followed by monkey atrium (86.3 percent), human atrium (71.7 percent), guinea pig atrium (48.7 percent), and monkey ventricle (30.1 percent). The sensitivity to 5-HT, measured as the negative logarithm of the half-maximal inotropic molar contractions of 5-HT, i.e., -logEC(50), was highest in the human atrium (6.65 +/- 0.20), followed by guinea pig atrium (5.53 +/- 0.36), monkey ventricle (4.83 +/- 0.28), guinea pig ventricle (4.56 +/- 0.11), and monkey atrium (4.46 +/- 0.16). The inotropic effects of 5-HT seen in the atrial and ventricular muscles of guinea pigs were abolished in the presence of the beta-receptor blocker, pindolol (8 mu M), while these effects in human atrial muscles and monkey atrial and ventricular muscles were abolished only in the presence of both pindolol (8 mu M) and of prazosin (1 mu M), an alpha(1)-receptor blocker. 5-HT increased the V(max) of the slow response recorded from guinea pig ventricular muscles exposed to high K+ (27 mM) media, whereas this agent did not alter the calcium current of isolated guinea pig ventricular myocytes devoid of sympathetic nerve terminals. In reserpinized guinea pig hearts, 5-HT exerted no inotropic effect on ventricular muscle, yet it had an inotropic effect in the atrial muscle, although the latter effect was considerably depressed, compared to that seen in non-reserpinized atrial muscles. We conclude that the positive inotropic effects of 5-HT observed in the ventricular muscle of the guinea pig and in the atrial and ventricular muscles of the Japanese monkey can be attributed to the release of noradrenaline from sympathetic nerve terminals (indirect effect). In contrast, in human atrial muscles, the positive inotropic effect of 5-HT was apparently the result of stimulation of a specific membrane receptor for 5-HT (direct effect). In guinea pig atrial muscles, both direct and indirect effects of 5-HT were involved in the positive inotropism. An explanation for the lack of sensitivity of rat atrial and ventricular muscles to 5-HT awaits further studies.