The direct negative chronotropic action of prazosin on the canine sinus node

The direct and indirect chronotropic effects of prazosin were studied in 22 anesthetized dogs using the technique of selective perfusion of the sinus node. Concentrations of 1, 10, 50 and 100 micrograms/ml of prazosin produced cumulative, dose-related reductions in mean sinus rat of 4 +/- 2; 10 +/- 6; 15 +/- 9 and 27 +/- 15 beats/min, respectively (P less than .0001). Intranodal prazosin did not significantly alter the positive chronotropic sinus node response to norepinephrine (0.05 and 0.1 micrograms/ml) administered via the same route. Sinus rate increases during stimulus frequency response curves after right stellate stimulation were not influenced by prior administration of prazosin. Sinus bradycardia elicited by submaximal vagal stimulation also was not affected by intranodal prazosin.l In six reserpinized dogs, methoxamine (10 and 25 micrograms/ml) injected into the sinus node artery caused a sinus rate increase of 10 4/- 2 and 14 +/- 3 beats/min (P less than .001). Intranodal prazosin (50 micrograms/ml) prevented this effect. Taken together, these results indicate that prazosin exerts a direct negative chronotropic action on the canine sinus node and that this effect is at least in part mediated through interference with alpha-1 receptors located in or near the sinus node. Prazosin has little or no effect on the presynaptic alpha-2 receptors nor does it interfere with the cholinergic mechanism in the sinus node.