Existence of beta(3)-adrenoceptors in rat heart: functional implications.

ABSTRACT

1. beta(3)-Adrenoceptors (AR) have been reported to be present in numerous species, where they mediate multiple responses. 2. The aim of the present study was to determine whether beta(3)-AR are present in intact rat heart and the functional implications of beta(3)-AR stimulation. The response to the cardiac beta(3)-AR-selective agonist BRL37344 was expressed as the percentage of values measured at baseline. 3. BRL37344 induced dose-dependent negative inotropic effects at concentrations ranging from 10(-11) to 10(-7) mol/L. BRL37344 (10(-8) mol/L) induced a decrease of left ventricular developed pressure (LVDP) from 127 +/- 5 to 89 +/- 16 mmHg (69 +/- 15%; P < 0.01) and +dP/dt from 2594 +/- 59 to 1885 +/- 50 mmHg/s (72 +/- 8%; P < 0.01). Moreover, a significant reduction of -dP/dt from 2176 +/- 42 to 1458 +/- 43 mmHg/s (67 +/- 8%; P < 0.01) was observed. The BRL37344 dose-response curves were not altered by nadolol (10(-5) mol/L), a potent beta(1)- and beta(2)-AR antagonist, but were completely suppressed by the addition of SR59230A (10(-5) mol/L), a potent beta(3)-AR antagonist. 4. The present study provides functional evidence for the presence of beta(3)-AR in rat hearts and shows, for the first time, that a highly specific beta(3)-AR antagonist can block the attenuation of LVDP caused by the specific beta(3)-AR agonist BRL37344 in rat beating hearts.