The effects of increasing intravenous (i.v.) doses of prazosin, phenylephrine, flecainide, and UK- 52,046 on blood pressure (BP), heart rate (HR) and the specialized conduction system (AH and HV intervals) were investigated in anaesthetized dogs. Results indicated that UK-52,046 (1-8 µg/kg) had no effect on BP or HR, but reduced (p<0.05) BP at doses of 16 and 32 µg/kg; no change occurred in HR. During sinus rhythm (SR) the AH or HV intervals did not change as compared with placebo; on pacing (PA) UK-52,046 (4-16µg/kg) decreased the AH interval. After prazosin BP decreased (p<0.05) after 20-40 µg/kg; HR increased after all doses (5-40 µg/kg). The HV interval was unaltered, but the AH interval decreased after 40 µg/kg during SR and PA. After phenylephrine (continuous infusion, 50 µg/ml/min) BP increased at 33 min and HR was decreased at 23 and 33 min. The AH interval lengthened during PA (p<0.05), but there was no effect on the HV interval. Administration of flecainide (0.5-2.0 mg/kg) had no effect on BP or HR but increased the HV interval during SR and PA (1 and 2 mg/kg, p < 0.05). The results indicate that the α1-adrenoceptor agonist phenylephrine and the α1-adrenoceptor antagonist prazosin, on PA altered the AH (but not the HV) intervals in opposite directions in association with changes in HR and BP. However, the new α1adrenoceptor antagonist UK-52,046 at doses that did not reduce BP or HR (4 and 8 µg/kg) and that also are antiarrhythmic (2-8 µg/kg) (1) differed from prazosin in that during SR the AH interval was not affected, although the AH interval was directly affected on PA
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