|Stoschitzky K et al.|
Different Effects of Propranolol, Bisoprolol, Carvedilol and Doxazosin on Heart Rate, Blood Pressure, and Plasma Concentrations of Epinephrine and Norepinephrine
Journal of Clinical and Basic Cardiology 2003; 6 (1-4): 69-72
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Keywords: Alphablockade, Betablockade, Bisoprolol, Blutdruck, Carvedilol, Doxazosin, Epinephrin, Herzfrequenz, Kardiologie, Norepinephrin, plasma, Propranolol, Sympathikus, Alphablockade, Betablockade, Bisoprolol, blood pressure, cardiology, Carvedilol, Doxazosin, epinephrine, heart rate, norepinephrine, plasma, Propranolol, Sympathikus
Background: Despite of its beta-blocking effects, carvedilol has been shown not to decrease resting heart rate in healthy subjects. Therefore, we compared haemodynamic effects of carvedilol (an alpha- and beta-blocker), propranolol (a non-selective beta-blocker), bisoprolol (a beta1-selective beta-blocker), doxazosin (an alpha-blocker) and placebo, at rest and during exercise. In addition, we measured plasma levels of epinephrine and norepinephrine. Methods: Twelve healthy males received single oral doses of 80 mg propranolol, 5 mg bisoprolol, 50 mg carvedilol, 4 mg doxazosin and placebo according to a randomized, double-blind, crossover protocol. Three hours after drug intake, heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. At the same times, plasma concentrations of epinephrine and norepinephrine were determined by HPLC. Results: At rest, propranolol (-21 %, p < 0.05) and bisoprolol (-21 %, p < 0.05) decreased heart rate, doxazosin (+30 %, p < 0.05) increased heart rate, whereas carvedilol had no effect. During exercise, propranolol (-26 %, p < 0.05), bisoprolol (-19 %, p < 0.05) and carvedilol (-18 %, p < 0.05) decreased heart rate, whereas doxazosin (+6 %, p < 0.05) increased heart rate. During exercise, plasma levels of norepinephrine with doxazosin were higher than those with propranolol and bisoprolol (p < 0.05 in both cases). Conclusions: These data show that "pure" beta-blockers decrease heart rate in healthy subjects even at rest. On the other hand, alpha-blockers increase heart rate, most likely caused by an increase of sympathetic tone as a physiological reaction to the blood pressure lowering effect of alpha-blockade. In carvedilol, which combines alpha- and beta-blockade in one molecule, these effects widely appear to compensate each other, thus resulting in a lack of effect on resting heart rate in healthy subjects. This low clinically effective beta-blockade of carvedilol at rest might explain the low incidence of side effects resulting from beta-blockade as well as the lack of effect of carvedilol on melatonin release. The slight differences between plasma levels of norepinephrine with doxazosin on the one hand and with propranolol and bisoprolol on the other hand give a weak support to the hypothesis that an increase of sympathetic tone caused by a decrease of blood pressure by alpha-blockade might weaken the net beta-blocking effects of carvedilol.