Exercise and Hypertension
March 2007
What is the relationship between nitric oxide and exercise?
Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and
transforming growth factor-beta(1) (TGF-beta(1)) mRNA increase in rat skeletal muscle in
response to a single acute exercise bout.  Nitric oxide (NO) is released locally by muscle
vascular endothelium and muscle fibers during exercise, contributes to the blood flow response
to exercise, and regulates mitochondrial respiration. Researchers found that nitric oxide
synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise. [3]

Why are endothelial function and nitric oxide so important to our health?
Normal endothelial function is very important to vascular health. The endothelium produces
numerous vasodilator and vasoconstrictor compounds that regulate vascular tone; the
vasodilator, nitric oxide has additional antiatherogenic properties, is probably the most
important and best characterized mediator, and its intrinsic vasodilator function is commonly
used as a surrogate index of endothelial function. Many conditions, including atherosclerosis,
diabetes mellitus and even vascular risk factors, are associated with endothelial dysfunction,
which, in turn, correlates with cardiovascular mortality. Furthermore, clinical benefit and
improved endothelial function tend to be associated in response to interventions. [4]

However, researchers also found that increased availability of nitric oxide substrate does not
enhance exercise-induced vasodilation in healthy subjects. [6]

How does exercise benefit our health?
Shear stress on endothelial cells is a potent stimulus for nitric oxide production. It has been
found that exercise training involving repetitive bouts of exercise over weeks up-regulates
endothelial nitric oxide bioactivity. Animal studies have found improved endothelium-dependent
vasodilation after as few as 7 days of exercise. Consequent changes in vasodilator function
appear to persist for several weeks but may regress with long-term training, perhaps reflecting
progression to structural adaptation which may, however, have been partly
endothelium-dependent. The increase in blood flow, and change in haemodynamics that occur
during acute exercise may, therefore, provide a stimulus for both acute and chronic changes in
vascular function. Substantial differences within species and within the vasculature appear to
exist. [4]

In humans, exercise training improves endothelium- dependent vasodilator function, not only as
a localized phenomenon in the active muscle group, but also as a systemic response when a
relatively large mass of muscle is activated regularly during an exercise training program. [4]

Individuals with initially impaired endothelial function at baseline appear to be more responsive
to exercise training than healthy individuals; that is, it is more difficult to improve already normal
vascular function. Improvement is reflected in increased nitric oxide bioactivity. In summary,
epidemiological evidence strongly suggests that regular exercise confers beneficial effects on
cardiovascular health. Shear stress-mediated improvement in endothelial function provides
benefits for cardiovascular health via exercise training. [4]

Exercise is good for health.


[1] McConell GK. Effects of L-arginine supplementation on exercise metabolism. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):46-51. [2]
Kohli R, et al, Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J
Nutr. 2004 Mar;134(3):600-8. [3] Gavin TP, et al, Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to
exercise. J Appl Physiol. 2000 Apr;88(4):1192-8. [4] Maiorana A, et al, Exercise and the nitric oxide vasodilator system. Sports Med.
2003;33(14):1013-35. [5] Wennmalm A, et al, Acute supplementation with the nitric oxide precursor L-arginine does not improve
cardiovascular performance in patients with hypercholesterolemia. Atherosclerosis. 1995 Dec;118(2):223-31. [6] Gilligan DM, et al,
Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation. 1994 Dec;90(6):2853-8. [7] Quyyumi AA.
Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia? A double-blind comparison of
parenteral D- and L-arginine. J Am Coll Cardiol. 1998 Oct;32(4):904-11. [8] Kawano T, et al, Supplementation of L-arginine improves
hypertension and lipid metabolism but not insulin resistance in diabetic rats. Life Sci. 2003 Oct 24;73(23):3017-26. [9] Suzuki J. L-arginine
supplementation causes additional effects on exercise-induced angiogenesis and VEGF expression in the heart and hind-leg muscles of
middle-aged rats. J Physiol Sci. 2006 Feb;56(1):39-44.
How does exercise improve our health?
Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise,
contributes to the blood flow response to exercise, and regulates mitochondrial respiration.

Does L-arginine help lower blood pressure?
L-arginine is the substrate for the enzyme nitric oxide synthase
(NOS), which is responsible for the endothelial production of
nitric oxide.

What is the impact of high systolic blood pressure?
Studies have shown that systolic blood pressure is an important indicator for cardiovascular diseases.

What is right-brain stroke?
With a left-brain stroke, patients may have difficulty understanding words or speaking themselves. By
contrast, the symptoms of a right-brain stroke are much more subtle.
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