Exercise training in doxorubicin-induced heart failure: effects on the L-arginine-NO pathway and vascular reactivity

Cristiane Matsuura, Tatiana M.C. Brunini, Lenize C.M.M. Carvalho, Angela C. Resende, Jorge J. Carvalho, João Pedro Werneck de Castro, Antonio C. Mendes-Ribeiro

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Heart failure (HF) is the end-stage of cardiovascular disease and is associated with a high incidence of thrombotic events. Nitric oxide (NO) mediates vasodilation and prevents platelet activation, providing an important antithrombotic effect. The aim of this study was to investigate the effects of aerobic training on survival, platelet L-arginine-NO pathway, and vasodilator properties in doxorubicin (DOX)-induced HF. Sprague Dawley rats were randomly assigned to saline/sedentary (SAL/SED), saline/exercise (SAL/EX), DOX/sedentary (DOX/SED), and DOX/exercise (DOX/EX) groups. Four weeks after intraperitoneal DOX injection (1 mg/kg-1/d-1; 10 days), shortening fraction in DOX/SED and DOX/EX was significantly reduced. Treadmill exercise was performed during 6 weeks, 5 days/week-1, 30 minutes/day-1, 50% to 60% of maximum velocity. Survival was higher in DOX/EX (67%) than DOX/SED (33%). No differences were observed in intraplatelet L-arginine transport assessed by incubation with L- [3H]-arginine, nor in NOS activity measured by the conversion of L- [3H]-arginine into L- [3H]-citrulline among the groups. Vasodilation response to acetylcholine was impaired in DOX/SED and DOX/EX; in nitroglycerine, it was limited to DOX/SED. Aerobic training reduced mortality in DOX-induced HF animals and restored vascular smooth muscle relaxation properties. However, it did not ameliorate intraplatelet NO bioavailability and endothelial function during the period studied.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalJournal of the American Society of Hypertension
Issue number1
StatePublished - Jan 2010
Externally publishedYes


  • Exercise
  • doxorubicin
  • heart failure
  • nitric oxide
  • platelets

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine


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