Alpha1-adrenoceptor antagonists block the positive chronotropic effect of 6-nitrodopamine in the isolated rat right atrium.

6-Nitrodopamine (6-ND) released from isolated rat atria produces potent positive chronotropic actions. Direct negative chronotropic responses to some selective α1-adrenoceptor (AR) antagonists like prazosin have been reported. Since α1-AR antagonists inhibit 6-ND-induced smooth muscle contractions, we have hypothesized that negative chronotropism induced by α1-AR antagonists reflects 6-ND blockade. This study investigated whether selective α1-AR antagonists affect 6-ND-induced positive chronotropism in isolated rat atria. Alfuzosin at 10 nM did not affect the atrial rate, but at 100 nM, it significantly reduced the atrial rate. This effect was not observed in L-NAME (100 mM)-treated preparations or in atria from rats chronically treated with L-NAME. Alfuzosin (100 nM) significantly reduced the 6-ND-induced positive chronotropism without affecting the chronotropic responses to noradrenaline, adrenaline, or dopamine. Similar results were obtained with doxazosin (1-10 nM), tamsulosin (10-100 nM), and prazosin (1-10 nM). Isoprenaline induced concentration-dependent increases in atrial rate, which were not significantly affected by any of these α1-AR antagonists. The results demonstrated that α1-AR antagonists reduced atrial basal rate only at concentrations affecting the positive chronotropic effect of 6-ND, and this reduction was not observed when NO synthesis was blocked, indicating that the negative chronotropic effect may involve 6-ND receptor blockade.