title: Selective sensory denervation by capsaicin aggravates adriamycin-induced cardiomyopathy in rats.
abstract: Capsaicin-sensitive sensory nerves that contain calcitonin gene-related peptide (CGRP) contribute significantly to cardioprotective mechanisms. In this study, the possible role of capsaicin-sensitive afferent nerves in the development of congestive heart failure was examined in an established model of adriamycin-induced experimental cardiomyopathy in rats. Systemic treatment with capsaicin was utilized to deplete sensory neuropeptides from cardiac afferent nerves. Echocardiography was applied to assess the cardiac function in adriamycin-treated rats pretreated with capsaicin or its vehicle. In control rats, adriamycin treatment produced a reduction in the fractional shortening of the left ventricle and an increase in the ratio of the left atrial diameter and the aortic diameter, indicative of a decreased myocardial contractility and heart failure only at 3-4 weeks post-treatment. In contrast, in capsaicin-pretreated rats, a deterioration of the cardiac function was already evident 1 week after the cessation of adriamycin administration, while the clinical signs associated with cardiomyopathy were more severe and displayed a significantly more rapid progression. Immunohistochemistry revealed a complete depletion of calcitonin gene-related peptide from cardiac sensory nerves after systemic capsaicin treatment. This study has demonstrated that elimination of capsaicin-sensitive afferent nerves promotes the development and progression of adriamycin-induced myocardial dysfunction. The results suggest that interfering with capsaicin/vanilloid receptor function and/or perturbation of the myocardial CGRP metabolism may open up new perspectives concerning prevention and/or alleviation of the pathological changes that follow adriamycin treatment.
authors.affiliation: Department of Pediatrics, University of Szeged, Korányi fasor 14-15, 6725 Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Katona
authors.forename: Krisztina
authors.initials: K
authors.lastname: Boros
authors.forename: Péter
authors.initials: P
authors.lastname: Sántha
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: Mária
authors.initials: M
authors.lastname: Dux
authors.forename: Gábor
authors.initials: G
authors.lastname: Jancsó
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000633:toxicity*; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000503:physiopathology*; D003714:Denervation / Q000379:methods*; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004317:Doxorubicin; D002211:Capsaicin