Cardiac electrophysiological effects of rilmenidine, a novel antihypertensive agent, in the conscious dog : Comparison with clonidine

Abstract

The cardiac electrophysiological effects of rilmenidine, a novel antihypertensive agent, and clonidine were studied in the conscious dog. Sinus rate, corrected sinus recovery time (CSRT) and Wenckebach point (WP) were measured in seven intact dogs. Atrial rate and atrial effective refractory period (AERP) were measured in six atrioventricular (AV)-blocked dogs with ventricular pacing. In both groups, blood pressure was also monitored. Each dog received with at least a three-day interval rilmenidine as dihydrogen phosphate and clonidine as hydrochloride in four successive intravenous injections, 30 min apart. In intact dogs, rilmenidine was administered at 50, 50, 100 and 200 μg/kg and clonidine at 2.5, 2.5, 5 and 10 μg/kg. In AV-blocked dogs, doses of rilmenidine were 25, 25, 50 and 100 μg/kg, those of clonidine 5, 5, 10 and 20 μg/kg. Rilmenidine and clonidine decreased sinus rate and atrial rate from the first dose. In this regard, rilmenidine was respectively 24 and 23 times less potent than clonidine. A lengthening of CSRT was observed at all doses with rilmenidine and at the last three doses with clonidine (ratio : 17) and a lowering of WP at all doses with rilmenidine and clonidine (ratio : 22). A shortening of AERP was also seen with rilmenidine and clonidine from the second dose (ratio : 6). All these effects may at least partly be explained by a cholinergic activation mechanism. In intact dogs both drugs produced a lowering of mean blood pressure (ratio : 17), whereas in AV-blocked dogs, in which ventricular rate was kept constant by pacing, pressure effects were more complex, being the resultant of hypotensive and hypertensive effects, the latter due to alpha vascular stimulation. Taken together, these results indicate that in the conscious dog, rilmenidine and clonidine exert qualitatively identical electrophysiological effects, but with different potency ratios.