Differential effects of urapidil and doxazosin on heart rate.
OBJECTIVE
Although alpha-blockers are effective in lowering blood pressure, they may increase heart rate, an unwanted effect that could negatively affect outcome. However, the alpha-blocker urapidil might not increase heart rate due to its additional effect on 5-HT1A receptors. Therefore, we compared the effects of urapidil on heart rate with those of another alpha-blocker, doxazosin.


METHODS
We performed a randomised, double-blind, placebo-controlled, cross-over study in 12 healthy males who received single oral doses of 60 mg urapidil, 4 mg doxazosin and placebo. Four hours following drug intake, heart rate and blood pressure were measured at rest and during exercise.


RESULTS
Both doxazosin and urapidil decreased blood pressure to the same extent. Compared to placebo, resting heart rate was significantly increased by doxazosin (+25%, P < 0.05) but not by urapidil (+12%, n.s.). Resting heart rate with doxazosin was significantly higher than with urapidil (P < 0.05). Similarly, the rate pressure product (RPP) at rest was increased by doxazosin (+17%, P < 0.05) but not by urapidil (+6%, n.s.).


CONCLUSIONS
We conclude that the increase in heart rate caused by urapidil is less pronounced than that with doxazosin, a property that might favour urapidil in the treatment of arterial hypertension. In addition, only doxazosin (but not urapidil) increased the RPP at rest, a finding that might be helpful to explain why this drug was never shown to improve outcome in the treatment of arterial hypertension.
Stoschitzky
Kurt
K
Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. kurt.stoschitzky@meduni-graz.at
Stoschitzky
Gergana
G
Wonisch
Manfred
M
Brussee
Helmut
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017292:Doxazosin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; C015568:urapidil; D017292:Doxazosin