Effects of selective dopaminergic receptor stimulation on ventricular remodeling after experimental myocardial infarction in rats.

BACKGROUND

The disappointing results of the nonselective dopaminergic agonist ibopamine in the treatment of heart failure may be caused by nonselective receptor stimulation. Therefore, a search for more selective dopaminergic agonists remains important. Z1046 is such a compound.

METHODS AND RESULTS

Forty-two normotensive rats with a myocardial infarction (MI) and 18 sham-operated rats were studied. Rats with MI were treated for 6 weeks with Z1046 (n = 12) or ibopamine (n = 12) or were not treated (n = 18). Sham-operated control rats were not treated (n = 18). Assessments during the trial included those of plasma catecholamine levels, cardiac function, and morphology. Z1046 significantly decreased heart rate and blood pressure in rats with MI. Ibopamine affected only blood pressure. Compared with control rats with MI (736 +/- 66 pg/mL), plasma norepinephrine was significantly lower both after Z1046 (508 +/- 44 pg/mL) and after ibopamine (561 +/- 28 pg/mL). Infarct size was significantly reduced both by Z1046 and by ibopamine (P < .05). Z1046, but not ibopamine, normalized baseline left ventricular pressure (P < .05, treated rats vs MI control rats).

CONCLUSIONS

The new (relatively selective) dopaminergic agonist Z1046 appears to have a more pronounced effect in protection against remodeling than ibopamine; this results in preservation of cardiac function. The effects appear to be mediated by both a reduced sympathetic drive and an improved hemodynamic profile.