Alpha1-adrenoceptor antagonists act in the rat isolated right atrium as 6-nitrodopamine receptor antagonists

Mouse right atrium expresses α _1A- , α _1B- and α _1D- adrenoceptor mRNAs and the positive inotropic and chronotropic actions induced by the selective α ₁ -adrenoceptor agonist phenylephrine were partially decreased by propranolol, and abolished when associated with prazosin. Endothelium-derived 6-nitrodopamine has potent positive chronotropic effect on the rat isolated right atrium and β-1 adrenoceptor antagonists only reduced the frequency of the rat isolated right atrium at the concentrations that blocked the chronotropic positive effect induced by 6-nitrodopamine. Here it was evaluated the effect of selective α ₁ -adrenoceptor antagonist tamsulosin, doxasozin, and alfuzosin on the positive chronotropic effects induced by 6-ND in the rat isolated right atrium. Euthanasia was carried out by administering an overdose of isoflurane (greater than 5%) until one minute after breathing ceased. Following euthanasia, the heart was removed, and the right atrium was isolated. It was then mounted between two metal hooks in custom-made 10-mL glass chambers filled with Krebs-Henseleit solution (KHS), continuously aerated with a 95% O2 and 5% CO2 mixture at 37°C, maintained by a heated circulator and coupled to a PowerLab Acquisition System. Alfuzosin at 10 nM (30 min) did not alter the basal atrial rate. At 100 nM it caused a significant fall in atrial rate. Incubation of the atria with 6-ND (1 pM) caused a significant increase in atrial rate, which was not affected when the atria was incubated with alfuzosin 10 nM, but significantly reduced when incubated with alfuzosin 100 nM. In atria pre-treated with D-NAME (100 µM), but not with L-NAME (100 µM), alfuzosin at 100 nM induced significant fall in atrial basal rate. In atria obtained from animals chronically treated with L-NAME, incubation with alfuzosin at 100 nM did not affect the basal atrial rate (Fig. 1F). Incubation with alfuzosin at 100 nM and 1 µM had no effect on the positive chronotropic effects induced by adrenaline (10 nM – 100 µM), noradrenaline (10 nM – 100 µM), and dopamine (10 nM – 100 µM). Similar results were observed with doxazosin and tamsulosin. The results clearly demonstrate that the alpha1-adrenoceptor antagonists cause fall in atrial rate due to blockade of 6-ND receptor.

This research is supported by the São Paulo Research Foundation (FAPESP).

This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.