Short-term electrophysiological effects of losartan, bisoprolol, amlodipine, and hydrochlorothiazide in hypertensive men.
OBJECTIVE
Hypertension-induced left ventricular structural remodelling associates with repolarization abnormalities. We investigated if antihypertensive drugs can modulate ventricular repolarization.


METHODS
A total of 183 hypertensive men received for 4 weeks drugs (losartan 50 mg, bisoprolol 5 mg, amlodipine 5 mg, hydrochlorothiazide (HCTZ) 25 mg) in a randomized order, separated by 4-week placebo periods. Electrocardiograms (ECG) were recorded at the end of placebo and drug periods. Measurements of repolarization duration (QT intervals), repolarization heterogeneity (T-wave peak to T-wave end (TPE) intervals), and T-wave morphology (T-wave principal component analysis (PCA) ratio, T-wave morphology dispersion (TMD), and total cosine R-to-T (TCRT)) during each drug were compared to placebo measurements.


RESULTS
Losartan and bisoprolol shortened maximum and mean rate-adjusted QT intervals as well as mean TPE interval, decreased TMD, and increased TCRT. Losartan also shortened precordial maximum TPE interval and decreased PCA ratio. Amlodipine had no repolarization effects, whereas HCTZ prolonged precordial maximum TPE interval and mean TPE interval.


CONCLUSIONS
Losartan and bisoprolol have beneficial short-term ECG repolarization effects. Amlodipine seems to have no repolarization effects. HCTZ seems to prolong the ECG TPE interval, potentially reflecting increased repolarization heterogeneity. These findings show that antihypertensive drugs may relatively rapidly and treatment-specifically modulate ECG markers of ventricular repolarization.
Porthan
Kimmo
K
Helsinki University Central Hospital, Helsinki, Finland. porthan@mappi.helsinki.fi
Viitasalo
Matti
M
Hiltunen
Timo P
TP
Vaananen
Heikki
H
Dabek
Juhani
J
Suonsyrja
Timo
T
Hannila-Handelberg
Tuula
T
Virolainen
Juha
J
Nieminen
Markku S
MS
Toivonen
Lauri
L
Kontula
Kimmo
K
Oikarinen
Lasse
L
D000200:Action Potentials; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017298:Bisoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D004594:Electrophysiology; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D016276:Ventricular Function / Q000187:drug effects*
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D019808:Losartan; D017298:Bisoprolol