Exercise training in doxorubicin-induced heart failure: effects on the L-arginine-NO pathway and vascular reactivity.
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 (1mg/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), 30minutes/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- [(3)H]-arginine, nor in NOS activity measured by the conversion of L- [(3)H]-arginine into L- [(3)H]-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.
Matsuura
Cristiane
C
Laboratório de Transporte de Membrana, Departamento de Farmacologia e Psicobiologia, UERJ, Brazil.
Brunini
Tatiana M C
TM
Carvalho
Lenize C M M
LC
Resende
Angela C
AC
Carvalho
Jorge J
JJ
de Castro
João Pedro Werneck
JP
Mendes-Ribeiro
Antonio C
AC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004452:Echocardiography; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D010976:Platelet Count; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D004317:Doxorubicin; D001120:Arginine; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000109:Acetylcholine