Arterial Stiffness, Elevated Blood Pressure, and Aging

Like skin, the walls of blood vessels lose their elasticity over the course of aging. Mechanisms involved in this loss include rising levels of long-lived cross-links in the extracellular matrix, wherein metabolic byproducts such as glucosepane glue together proteins and so alter the structural properties of important tissues. Our biochemistry struggles to break these cross links and so they accumulate as a consequence of the natural operation of metabolism. In blood vessels the consequences of loss of elasticity become increasingly serious over time, as this is a part of a feedback loop of dysfunction in the cardiovascular system that causes hypertension, heart abnormalities, and damage to blood vessels and surrounding tissues throughout the body. All of this could be dialed back just by maintaining elasticity in blood vessels, which would involve the development of treatments to clear cross-links, among other items, a field of research that sadly sees little funding and interest given its potential:

Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naïve.

The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short- and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level.

Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of the hemodynamic changes with aging makes the "one-size-fits-all" approach suboptimal and urges for therapies that address the vascular profile that underlies a given blood pressure, rather than the blood pressure values themselves.



To maintain endothelial lining, how about just eating foods high in nitrates, then test several times a day with nitric oxide test strips. Nitrates are absorbed in digestion, then produce nitrites in saliva when combined with bacteria. Nitrites are swalled and are precursors to nitric oxide. In my N=1 experiments, arginine and citrulline utterly failed to increase my nitric oxide levels. But nitrate rich foods substantially move the needle on the test strips.

Posted by: pone at February 21st, 2015 3:06 AM

@ the previous commentator: The N=1 experiment with nitrate rich foods is interesting. I, too use arginine regularly, but I test the effects with regularly checking central arterial compliance (we have in my lab developed a new method for non-invasive determination of compliance and TPR). Will take your suggestion and put it to the test, too. For good replication it would be interesting to know which types of foods you used.

Posted by: Lutz Kraushaar at February 23rd, 2015 2:19 AM

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