Rise in serum angiotensin 2 levels related to exercise

High blood pressure (hypertension) indicates the deterioration of the set
points of metabolic fitness and is one of the most frequent metabolic risk
factors in Western countries. A major target of the current pharmacological
treatments involves the inhibition of the enzyme angiotensin-converting enzyme
(ACE), which lowers the serum levels of the vasoconstrictor angiotensin II
(AngII) and develops a generally positive effect on mortality. Based on only
one study ACE inhibitors are now even considered to prevent sarcopenia and
physical decline in the elderly. These recently voiced beliefs do not match the
physiological effects that are found in humans. It has been identified that
genetic and pharmacological inhibition of ACE activity can be detrimental for
metabolic fitness and possibly strength in men. ACE inhibition can reduce cross
section of muscle fibers and genetic inhibition of ACE can manifest in reduced
trainability of aerobic fitness.
The negative impact of ACE inhibition on metabolic function in man may be
explained by the *double* role of the product of ACE action, AngII, in
vasoconstriction and capillary growth (angiogenesis). In resting muscle, the
role of AngII is to restrict blood from entering non-active muscles. The
AngII-mediated vasoconstriction is overridden with the onset of contraction
through flow-induced dilatation of conduit arteries and arterioles and is
expected to promote angiogenesis by activating the endothelial cell population
that constitutes the capillary wall. Different studies support the notion that
a switch in AngII action from arterioles to the endothelium of the perfused
vessel lumen facilitates exercise-induced capillary growth in human skeletal
muscle.
An interaction between physical activity and angiotensin 2-mediated
angiogenesis may also explain the large differences in therapeutic efficiency
of current anti-hypertensive treatment. Genotypic variants of ACE with lowered
serum angiotensin 2 due to the presence of the *I-allele* which silences ACE
expression show lowered gains in maximal oxygen uptake with exercise
rehabilitation. Transcript expression of pro-angiogenic factors, which reflects
the mechanism that instructs the elevation in muscle capillarity, after
exercise is reduced in genotypes being homozygous (ACE-II) or heterozygous
(ACE-ID) for the *I-allele*.
Awareness of the existence of such a mechanism could develop major economic and
clinical repercussions on current Health Care practice. Pharmacological
inhibition of AngII action may have undesirable side effects, particularly, in
the situation when one wants to exploit the sympatholytic and angiogenic
benefits of physical therapy. This activity-dependent mechanism has rarely been
valued in pharmacological studies of hypertension
We aim to expose the pathway by which AngII is implicated in exercise-induced
capillary growth of human muscle. We hypothesize that the blunting of AngII
production with concomitant exercise reduces improvements in metabolic fitness
by removing an important stimulus for capillary growth in exercised muscle.

The aim of this study is to find out at what moment in time during, or after,
short high intensity or prolonged low intensity exercise there is a significant
rise in serum AngII levels.

The study is an cross-sectional study.

The subjects will perform an incremental exercise test, a low intensity
exercise test and a high intensity exercise test on separate occasions. The
later 2 tests will be performed in random order. The duration of the data
collection phase will be approximately 3 weeks.

Subjects will visit the VU University Amsterdam on three separate occasions.
Testing will take about an hour each time. The exercise tests will entail a
degree of effort and fatigue but this will not be excessive or prolonged and is
something that the participants will be able to go through. Participants will
be constantly monitored before, during and after all tests and will be made
aware that they may withdraw from the study at any time. An intravenous cannula
will be inserted into a vein in the subjects arm for obtaining blood samples.
This may cause a brief discomfort for some subjects. There is a small risk of
infection when inserting the cannula. To minimize the risk, the cannula will be
inserted and the blood samples will be drawn by a qualified phlebotomist with
the use of sterile equipment. In total eighteen 2 ml blood samples (six per
test) per person will be withdrawn.