Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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accompanied by reduced baroreflex sensitivity, increased sympathetic and reduced

parasympathetic activity and increased blood pressure variability, important mark-

ers of autonomic dysfunction [ 66 ].

2.2 Correction of Autonomic Dysfunction by Exercise

Training

Aerobic exercise training is recognized as one of the most efficient non-

pharmacological therapeutic strategies, producing in hypertensive patients an arte-

rial pressure reduction in the range of 8–5 mmHg [ 67 , 68 ]. In the 3-months old

SHR, 6–8 weeks of moderate aerobic exercise training (5 sessions per week, 1 h per

session and 50–60% of maximum exercise capacity) are able to significantly

decrease mean arterial pressure by approximately 5–15% [ 3 , 46 , 69 , 70 ]. However,

pressure fall is partial and pressure levels are still higher in the trained SHR when

compared to sedentary age-matched normotensive controls. Similar data were

observed in the renovascular model of hypertension [ 71 , 72 ].

Besides the beneficial remodeling of the microcirculation in exercised tissues

(capillary angiogenesis, wall/lumen ratio normalization of the hypertrophied arteri-

oles, increased conductance of small venules, [ 73 – 77 ]), training-induced regression

of autonomic dysfunction is considered one of the most important mechanism for

the correction of hypertension-induced deleterious adjustments, in addition to the

partial blood pressure fall. In the adult SHR only 1–2 weeks of aerobic training are

able to downregulate brain RAS [ 2 ] and to reduce oxidative stress and inflammatory

profile in brain autonomic areas [ 3 , 66 ], therefore normalizing baroreflex control of

the heart simultaneously with the reduction of pressure variability and augmenta-

tion of heart rate variability [ 2 , 3 , 66 ]. These autonomic benefits of exercise training

occur before the appearance of resting bradycardia and pressure fall (~5–8%, usu-

ally around the 4th week of training) and are significantly correlated with the reduc-

tion of angiotensinogen expression in the PVN [ 2 , 3 , 66 ]. Normalization of

baroreflex function associated to increased vagal cardiac activity contributes to rest-

ing bradycardia in hypertensive-trained rats. As a consequence, 2-weeks trained

SHRs present a near normal autonomic control, reduced sympathetic and elevated

cardiac vagal activity, even exhibiting high-pressure levels [ 2 , 3 ]. Improvement of

reflex bradycardia and decreased level of both oxidative stress and pressure were

also observed in the left ventricle and kidney of renovascular hypertensive rats sub-

mitted to 4 weeks of swimming training [ 71 ].

Previous experiments from our and other laboratories have shown that aerobic

training in SHR increases the sensitivity of aortic baroreceptors [ 78 ], augments the

density of noradrenergic ascending projections from NTS to preautonomic neurons

in the PVN [ 79 ], induces plastic changes and increases the density of oxytocinergic

neurons within autonomic PVN subnuclei [ 80 , 81 ], augments the intrinsic excit-

ability of these preautonomic neurons projecting to brainstem areas involved in the

G.S. Masson and L.C. Michelini