Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Abstract

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.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

“…Concentric cardiac hypertrophy might also result from pressure overload observed in many pathologic conditions, such as hypertension (8). However, this type of hypertrophy is followed by diastolic and/or systolic dysfunction and a disproportionate increase in the thickness of the left ventricle posterior wall and interventricular septum (8)(9)(10). Sometimes, the physiological hypertrophy developed by high level strength athletes presents a macroscopic structure similar to pathological hypertrophy, which could be incorrectly interpreted as pathological.…”

Aerobic exercise training in heart failure: impact on sympathetic hyperactivity and cardiac and skeletal muscle function

“…Indeed, exercise training reduced cardiac angiotensin II levels by reducing local renin-angiotensin system activation in HF α 2A / α 2C ARKO mice (21). This phenomenon was accompanied by a prominent reduction in both cardiac myocyte width and collagen deposition, which resulted in improved ventricular function in HF animals.…”

“…These effects include reduction of sympathetic outflow in exercised humans (14,15) and animals (16)(17)(18) with HF. The sympathetic toxicity of cardiac (17)(18)(19)(20)(21) and skeletal (22)(23)(24) muscles in HF is also reduced by exercise training. Since morbidity and mortality in cardiovascular disease are often associated with increases of sympathetic nerve activity, exercise training becomes a potent nonpharmacological strategy for HF therapy.…”

Role or Synergistic Interaction of Adenosine and Vitamin D3 Alongside High-Intensity Interval Training and Isocaloric Moderate Intensity Training on Metabolic Parameters: Protocol for an Experimental Study (Preprint)

“…The body weight and body length will be determined with the following anthropometrical parameters: _ Body mass index (BMI)=body weight(g)/length2 (cm 2 ). Lee index = cube root of body weight (g) / nose-to-anus length (cm) (Bernardis, 1970) [38].Specific rate of body mass gain (g/kg=dM/Mdt), Where, dM represents the gain of body weight during dt= t2_t1 and M is the rat body weight at t1.…”

“…Then, every rat will be placed on the treadmill to continue running at maximum speed up to the exhaustion point. Following the recording of the maximum speed during exhaustion for every rat, [38] the mean value of speed of the exercising rats will be calculated. Then, the exercise protocol will be designed [39], [ Table 1 …”