Electrophysiological responses to imidazoline/alpha2-receptor agonists in rabbit sinoatrial node pacemaker cells

To compare the effects of moxonidine (Mox), clonidine (Clo), agmatine (Agm), and xylazine (Xyl) on action potentials (AP) of the rabbit sinoatrial node (SAN) pacemaker cells and investigate the contribution of alpha-adrenoceptors to the cardiac electrophysiologic responses induced by the agonists.

Intracellular microelectrode technique was used to record AP in the rabbit SAN pacemaker cells. Vasoconstrictive responses to norepinephrine (NE), Mox, Clo, Agm and Xyl were observed in the thoracic aorta and ear vein isolated from rabbits.

(1) In the rabbit thoracic aorta, a rank order of potency producing vasoconstrictive responses was NE>Clo>Mox; and a rank order of potency in ear vein was Clo>NE>Xyl=Mox. Agm did not produce any vascular responses in both preparations, and Xyl did not produce vascular responses in the thoracic aorta. (2) Mox, Clo, Xyl, and Agm concentration-dependently decreased the rate of pacemaker firing (RPF), and prolonged APD50 and APD90 in the rabbit SAN pacemaker cells. The rank order of decreasing RPF or prolonging APD was Clo>Xyl=Mox. (3) Most effects of Clo were partially inhibited by yohimbine, but those of Xyl and all the effects of Agm on the AP in SAN pacemaker cells were not affected by the treatment with yohimbine. (4) In the presence of propranolol 1 micromol/L, phenylephrine did not cause any effects on AP in the rabbit SAN pacemaker cells.

Like Mox, Clo changes AP of the rabbit SAN pacemaker cells via alpha2-adrenoceptors partially, but the effects of Xyl and Agm on the AP are almost not related to alpha2-adrenoceptors. Moreover, there are no obviously functional alpha1-adrenoceptors in the rabbit SAN pacemaker cells.