Effects of repeated footshock stress on the chronotropic responsiveness of the isolated pacemaker of the rat: role of beta-2 adrenoceptors.

The effects of repeated footshock stress on the chronotropic responsiveness of the isolated right atria were studied. Repeated footshock stress was found to produce supersensitivity to isoproterenol and epinephrine (increase of 4.6- and 1.99-fold at pD2 level, respectively), but not to norepinephrine. Experiments using salbutamol, in the presence of an effective blocking concentration of metoprolol, showed that footshock stress increases the sensitivity (2.69-fold at pD2 level) to the selective beta-2 adrenoceptor agonist. Footshock stress had no effect on the atrial sensitivity to theophylline (1.09-fold at pD2 level). Addition of butoxamine (1 microM) suppressed footshock-induced pacemaker supersensitivity to isoproterenol and epinephrine. Footshock stress causes a small (3.23-fold) but pharmacologically unimportant increase in pacemaker pA2 value of metoprolol. However, footshock stress induces a large increase in the pacemaker beta-2 adrenoceptor affinity for butoxamine (11.48-fold, pA2 value). It is concluded that repeated footshock stress acts primarily to increase the chronotropic function of pacemaker beta-2 adrenoceptors, thus causing supersensitivity to isoproterenol, epinephrine and salbutamol.