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Discrepant Regulation of QT ( QT c) Interval Duration by Calcium Channel Blockade and Angiotensin Converting Enzyme Inhibition in Experimental Hypertension
Author(s) -
Klimas Jan,
Vaja Vaclav,
Vercinska Miriam,
Kyselovic Jan,
Krenek Peter
Publication year - 2012
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2012.00901.x
Subject(s) - qt interval , blockade , renin–angiotensin system , angiotensin converting enzyme , calcium channel , pharmacology , duration (music) , calcium , angiotensin ii , enzyme , chemistry , medicine , blood pressure , biochemistry , receptor , art , literature
Antihypertensive treatment may reduce prolonged QT duration in hypertension. Generally, the reductions of blood pressure and/or of cardiac mass are believed to be the responsible factors. However, drugs are not equivalent in QT modulation despite similar antihypertensive and antihypertrophic action. We investigated the effect of a calcium channel blocker, lacidipine and an angiotensin‐converting enzyme inhibitor, enalapril on QT duration in rats. Normotensive W istar‐ K yoto rats ( WKY ) and spontaneously hypertensive rats ( SHR ) were treated with lacidipine (at the dose of 1.5 mg/kg per day for WKY and 3 mg/kg per day for SHR ) or enalapril (5 mg/kg per day for WKY and 10 mg/kg per day for SHR ) during 8 weeks. Tail‐cuff systolic blood pressure ( sBP ), left ventricular weight ( LVW ), vascular function of isolated aorta and mesenteric artery and duration of QT (and QT c) interval on Frank electrocardiograms were evaluated. As expected, untreated SHR showed elevated sBP , impaired vascular reactivity, increased LVW and prolonged QT when compared with WKY ( p < 0.05). After treatment, both agents markedly improved vascular reactivity and reduced sBP in SHR ( p < 0.05). Additionally, enalapril reduced LVW in both hypertensive (by 17%; p < 0.05) and normotensive rats (by 13%; p < 0.05) and, consequently, corrected QT duration in SHR . Interestingly, lacidipine also reduced LVW in SHR (by 9%; p < 0.05), but without influence on prolonged QT . Moreover, lacidipine had no effect on LVW in WKY s but prolonged their QT interval (by 10%; p < 0.05). In conclusion, lacidipine did not reverse a progressive prolongation of QT in SHR , despite sBP lowering and LVW reduction. Thus, the lowering of blood pressure and/or reduction of LVW are not sufficient per se to normalize ventricular repolarization in hypertensive cardiac disease. More likely, modulation of QT prolongation by antihypertensive drugs is a function of their complex action on blood pressure, vascular function, cardiac mass and on reflex neurohumoral activation.