Selective sensory denervation by capsaicin aggravates adriamycin-induced cardiomyopathy in rats.
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.
Katona
Márta
M
Department of Pediatrics, University of Szeged, Korányi fasor 14-15, 6725 Szeged, Hungary.
Boros
Krisztina
K
Sántha
Péter
P
Ferdinandy
Péter
P
Dux
Mária
M
Jancsó
Gábor
G
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
D004317:Doxorubicin; D002211:Capsaicin