Many control mechanisms exist which successfully match the supply of blood with the metabolic
demand of various tissues under wide-ranging conditions. One primary regulator of vasomotion
and thus perfusion to the muscle tissue is the host of chemical factors originating from the
vascular endothelium and the muscle tissue, which collectively sets the level of vascular
tone. With advancing age and in many disease states, deleterious adaptations in the
production and sensitivity of these vasodilator and vasoconstrictor substances may be
observed, leading to a reduction in skeletal muscle blood flow and compromised perfusion to
the muscle tissue. Adequate perfusion is particularly important during exercise to meet the
increased metabolic demand of the exercising tissue, and thus any condition that reduces
tissue perfusion may limit the capacity for physical activity. As it is now well established
that regular physical activity is a key component in maintaining cardiovascular health with
advancing age, there is a clear need for further studies in populations where vascular
dysfunction is compromised, with the goal of identifying the mechanisms responsible for the
dysfunction and exploring whether these maladaptations may be remediable. Thus, to better
understand the etiology of these vascular adaptations in health and disease, the current
proposal is designed to study changes in vascular function with advancing age, and also
examine peripheral vascular changes in patients suffering from chronic obstructive pulmonary
disease (COPD), Sepsis, Pulmonary Hypertension, and cardiovascular disease. While there are
clearly a host of vasoactive substances which collectively act to govern vasoconstriction
both at rest and during exercise, four specific pathways that may be implicated have been
identified in these populations: Angiotensin-II (ANG-II), Endothelin-1 (ET-1), Nitric Oxide
(NO), and oxidative stress.
Phase:
Phase 1
Details
Lead Sponsor:
Russell Richardson
Treatments:
Acetylcholine Angiotensin II Angiotensinogen cyclo(Trp-Asp-Pro-Val-Leu) Fexofenadine Giapreza Nitroprusside Norepinephrine Phentolamine Ranitidine Thioctic Acid Valsartan Vitamin E Vitamins