Endogenous Norepinephrine Desensitizes <i>α</i><sub>1D</sub>-Adrenoceptors in Cultured Rat Aorta

Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α1D-adrenergic receptor (α1D-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α1D-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α1D-AR antagonist) or 5-methylurapidil (α1A-AR antagonist) was used to identify the α1-AR involved in the response, or BMY-7378 to protect the α1D-AR from desensitization. Results showed that α1D-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α1D-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α1A-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α1B-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α1D-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α1D-AR in the cultured aorta, and the α1D-AR is protected by BMY-7378.