Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice.
The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3-5 month-old mice lacking alpha(2A-) and alpha(2C-)adrenoceptors (alpha(2A)/alpha(2C)ARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased alpha(2A)/alpha(2C)ARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.
Pereira
M G
MG
School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil.
Ferreira
J C B
JC
Bueno
C R
CR
Mattos
K C
KC
Rosa
K T
KT
Irigoyen
M C
MC
Oliveira
E M
EM
Krieger
J E
JE
Brum
Patricia Chakur
PC
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D009206:Myocardium / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D018754:Ventricular Dysfunction / Q000503:physiopathology
C547769:Adra2a protein, mouse; C547775:Adra2c protein, mouse; D018341:Receptors, Adrenergic, alpha-2; D000804:Angiotensin II