Rabbit, a relevant model for the study of cardiac β 3 ‐adrenoceptors

The β 3 ‐adrenoceptors (β 3 ‐ARs) have been identified and characterized in the human heart. Specific β 3 ‐AR stimulation, unlike β 1 ‐AR or β 2 ‐AR stimulation, decreases cardiac contractility, partly via the G i –NO pathway. However, the precise role of cardiac β 3 ‐ARs is not yet completely understood. Indeed, under normal conditions, the β 3 ‐AR response is present only to a very low degree in rats and mice. Therefore, we evaluated whether β 3 ‐ARs were present and functional in rabbit ventricular cardiomyocytes, and whether the rabbit could serve as a relevant model for the study of cardiac β 3 ‐ARs. We used RT‐PCR and Western blot to measure the β 3 ‐AR transcripts and protein levels in rabbit ventricular cardiomyocytes. We also analysed the effect of β 3 ‐AR stimulation using isoproterenol in combination with nadolol or SR 58611A on cardiomyocyte shortening, Ca 2+ transient, L‐type Ca 2+ current ( I Ca,L ), delayed rectifier potassium current ( I Ks ) and action potential duration (APD). For the first time, we show that β 3 ‐ARs are expressed in rabbit ventricular cardiomyocytes. The mRNA and protein sequences present a high homology to those of rat and human β 3 ‐ARs. Furthermore, β 3 ‐AR stimulation decreases cardiomyocyte shortening, Ca 2+ transient and I Ca,L amplitudes, via a G i –NO pathway. Importantly, β 3 ‐AR stimulation enhances I Ks amplitude and shortens the APD. Taken together, our results indicate that the rabbit provides a relevant model, easily used in laboratories, to study the roles of cardiac β 3 ‐ARs in physiological conditions.