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

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uncoupling), the endothelial function in SHR aortas being improved only by moder-

ate exercise intensity. Similar results were observed in health individuals [ 122 ].

Both high NO bioavailability and increased antioxidant enzymatic system are

proposed as the main mechanisms to reduce the expression of the vasoconstrictor

RAS axis and attenuate angiotensin II effects in vessel wall. In fact, gene and pro-

tein expression of angiotensinogen, angiotensin converting enzyme and AT1 recep-

tor are decreased in the aorta of trained SHR [ 118 ], training also  attenuated

angiotensin II’s vasoconstrictor effects in aorta of ovariectomized spontaneously

hypertensive rats independently of estrogen therapy [ 123 ]. Sequential measurements

of angiotensinogen expression (western blotting) and of the content of angiotensin II

and angiotensin (1–7) in the renal, femoral, carotid and thoracic aorta (high perfor-

mance liquid chomatrography) in adult SHR submitted to aerobic training revealed

that only 1–2 weeks are able to normalize the elevated angiotensinogen content in

the renal artery, which is accompanied by a parallel robust reduction of angiotensin

II concentration and a mild decrease in angiotensin-(1–7) content in renal artery

[ 70 ]. The differential responses of the vasoconstrictor and vasodilator RAS axes

result in a complete normalization of the angiotensin II/angiotensin-(1–7) ratio in

the renal arteries of the SHR at the 4th week of training, coinciding with the partial

but significant decrease in arterial pressure (5–6%). These vascular changes are

accompanied by similar responses of the intra-renal RAS axes [ 70 ]. In the other

SHR arteries, RAS expression is also depressed but training-induced decreases are

smaller and similar for both angiotensin II and angiotensin-(1-7) with unchanged

vasoconstrictor/vasodilator ratio within the femoral, carotid and thoracic aortas

[ 70 ]. Together these results showing similar training-induced time course RAS

changes for peripheral tissues and brain (previous section) indicate a broad and

prompt response to exercise in order to overcome the deleterious circulatory and

autonomic responses triggered by hypertension; they also suggest a wide effect of

aerobic training to downregulate both RAS axes, in order to maintain its equilibrium

in a lower level. The higher expression of angiotensin II and angiotensin-(1-7) in

renal arteries of sedentary SHR (over 30-fold when compared to other territories,

[ 70 ]) and the its marked reduction in trained rats confirm the important role of kid-

ney RAS changes in both the development as well as the regression of deleterious

hypertension-induced changes. Exercise training is also able to correct in the vascu-

lature the cellular responses associated with RAS hyperactivity as the oxidative

stress and pro-inflammatory profile [ 70 , 118 , 119 ].

Long-term exercise training (12  weeks) is effective in normalizing collagen

accumulation, MMP9 expression and fenestrae density therefore correcting the

stress x strain relationship in coronary and mesenteric arteries from SHR [ 119 ].

Also, trained SHRs present intact internal elastic lamina and attenuated collagen

gene expression in the aorta [ 124 ]. Although based on associative data, normaliza-

tion of mechanical properties (which reduces pulse wave velocity and pulsatility in

hypertensive arteries, [ 119 ]) seems to be related with cardiovascular benefits

observed in trained rats.

16 Experimental Evidences Supporting Training-Induced Benefits inflSpontaneously...