Selective sensory denervation by capsaicin aggravates adriamycin-induced cardiomyopathy in rats

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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.

Original languageEnglish
Pages (from-to)436-443
Number of pages8
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume370
Issue number6
DOIs
Publication statusPublished - Dec 1 2004

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Keywords

  • Adriamycin
  • Calcitonin gene-related peptide
  • Capsaicin
  • Cardiomyopathy
  • Cardioprotection
  • Echocardiography
  • Rat
  • Sensory nerves

ASJC Scopus subject areas

  • Pharmacology

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