Abstract
The functional role of beta(3)-adrenergic receptors in the heart is still not clear. The actions of two widely used beta(3)-adrenoceptor agonists, such as BRL 37344 and CGP 12177, were studied in the isolated guinea pig heart, perfused at constant pressure according to the Langendorff technique. Heart contractility (dP/dt, first derivative of pressure measured over time) and coronary flow (CF) were assessed simultaneously. BRL 37344 and CGP 12177A at a concentration range of 10-8-10-5 M increased dP/dt and CF. The selective beta(3)-antagonist L-748337 (10-6 M) did not significantly influence either BRL 37344 or CGP 12177A-induced responses. However, both dP/dt and CF responses to BRL 37344 and CGP 12177A at a concentration of 10-7 M were abolished in the presence of the beta(1)/beta(2)-antagonist nadolol (10-5 M). In contrast, cardiovascular responses to CGP 12177A at a higher concentration of 10-5 M were hardly inhibited by nadolol (10-5 M). In addition, BRL 37344 and CGP 12177A at concentrations as low as 10-8 M almost completely abolished an isoprenaline-induced increase in contractility, suggesting that both BRL 37344 and CGP 12177A display beta(1)-antagonistic properties. These data suggest that the stimulatory cardiovascular responses to BRL 37344 at a full range of concentrations, and CGP 12177A at a low concentration of 10-7 M, are not mediated by beta(3)-adrenergic receptors, but rather by activation of beta(1)- or beta(2)-adrenergic receptors. Cardiovascular effects of CGP 12177A at a high concentration of 10-5 M are independent of beta(1)/beta(2)/beta(3)-adrenergic receptors. Summing up, it seems that in the isolated guinea pig heart the functional role of beta(3)-adrenoceptors is not significant. Nonetheless, BRL 37344 and CGP 12177A are not ideal tools for investigation of beta(3)-adrenergic receptor-dependent effects, because these compounds interact with other types of beta-adrenergic receptors.
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