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

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Aerobic training is also able to reduce total peripheral resistance by normalizing

the vascular resistance of exercised tissues. A complete regression of increased arte-

riolar wall/lumen ratio in skeletal muscles, myocardium and diaphragm is observed

in trained SHRs, the decrease in arterioles wall/lumen ratio being positively

correlated with the reduction in both skeletal muscle vascular resistance and blood

pressure [ 73 – 75 , 77 , 125 ]. Data from these studies showing unchanged arterioles

wall/lumen ratio in tissues that respond with vasoconstriction to acute bouts of exer-

cise thus maintained elevated local vascular resistance [ 73 , 77 ] highlighted why

training reduce but does not normalize blood pressure levels. These vascular adapta-

tions combined with improved autonomic control and decreased sympathetic out-

flow, contribute to decrease the vascular response during lumbar nerve stimulation,

muscle contraction and dynamic submaximal exercise in trained hypertensive rats

[ 75 , 126 , 127 ]. Indeed, exercised-muscles in old trained rats exhibit attenuated

angiotensin II-induced vasoconstriction when compared to age-matched sedentary

controls [ 128 ].

Besides arterial and arteriolar adaptations, exercise training also increases the

density of small venules (cross-sectional area < 300 μm) in skeletal muscles [ 74 , 76 ]

and causes robust capillary angiogenesis in trained hypertensive animals [ 73 – 77 ,

109 , 129 – 132 ]. VEGF is recognized as the main molecular player in training-

induced angiogenesis and is rapidly (~3 days) activated by exercise training [ 129 ,

130 ]. Post-transcriptional regulation by miRNAs is also involved in the vascular

response to training: compared to sedentary hypertensive controls swimming-

training reduced the increased expression of miRNAs-16 and -21, and increased

that of miRNA-126 [ 130 ]. miRNA-16 and -126 interact directly and regulate the

activity of VEGF and PI3KR2 (a negative regulator of PI3K/Akt/eNOS pathway),

respectively [ 133 , 134 ]. In agreement with miRNAs’ changes, swimming-trained

hypertensive rats exhibit increased VEGF and eNOS protein levels, inhibiting capil-

lary apoptosis and restoring its density [ 130 ]. In fact, additional rise of capillary/

fiber ratio contributes to hypotensive additive effect in angiotensin-converting

enzyme inhibitor treated and trained hypertensive rats [ 131 , 132 ].

4 Conclusions

Development of hypertension in different experimental models is accompanied by

unbalance of the renin-angiotensin system, oxidative stress and inflammation that

trigger several autonomic and peripheral deficits. These deleterious hypertension-

induced cardiovascular deficits condition end-organ damage being important risk

factors for increased morbimortality in hypertensive subjects. As summarized in

Fig. 16.1, experimental studies provided extensive data demonstrating that

moderate- intensity exercise training is a crucial therapeutic tool to overcome most

of the deleterious hypertension-induced effects. It has potent and wide effects coun-

teracting/normalizing the cellular/molecular pathological mechanisms induced by

G.S. Masson and L.C. Michelini