Calcium channel blocker-induced protection against cardiovascular damage.
The therapeutic effects of calcium channel blockers on heart failure are controversial. However, a recent clinical trial demonstrated a favorable effect of amlodipine on survival rates in patients with heart failure resulting from nonischemic dilated cardiomyopathy. There are a number of studies showing that cytokines generated by activated immune cells cause an increase in nitric oxide (NO) via induction of NO synthase (NOS), which results in a direct negative inotropic effect and a modulation of inotropic responsiveness. Increases in inflammatory circulating cytokines have been detected in patients with heart failure and cardiomyopathy, elevated plasma levels of nitrite/nitrate in patients with heart failure have been reported, and inducible NOS (iNOS) has been found in ventricular tissue from patients with dilated cardiomyopathy. In our recent study, amlodipine improved histopathological lesions in the heart and survival rates in a murine model of nonischemic heart failure induced by encephalomyocarditis virus. Amlodipine inhibited NO production in vitro and decreased the number of iNOS positive cells in vivo. In this model, the therapeutic effect of amlodipine on myocardial injury is considered in part to result from inhibition of overproduction of NO. In this review, the possible roles of cytokines and NO in the pathophysiology of heart failure are discussed, along with the opportunities for therapeutic intervention.
Matsumori
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Department of Cardiovascular Medicine, Kyoto University, Japan. amat@kuhp.kyoto-u.ac.jp
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018188:Cardiovirus Infections / Q000150:complications; D016207:Cytokines / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D004686:Encephalomyocarditis virus; D006333:Heart Failure / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D051379:Mice; D009205:Myocarditis / Q000821:virology; D009569:Nitric Oxide / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D002121:Calcium Channel Blockers; D016207:Cytokines; D012333:RNA, Messenger; D017311:Amlodipine; D009569:Nitric Oxide; D004110:Diltiazem