In this context,
de Boer et al. suggest a Ceritinib cell line regulatory role for muscle PVAT around nutrient arterioles that may signal to the vessel wall, both locally (paracrine) and downstream (vasocrine), through outside-to-inside signaling. Finally Judy Muller-Delp and colleagues [5] seek new friends, new foes, and new clinical directions within the aging microcirculation, and explore emerging evidence that the reactive oxygen species H2O2 and ONOO˙− function as important signaling molecules in the aging microvasculature. Although the vasoactive and signaling properties of these ROS have been well-documented, relatively little work has been performed to determine whether these molecules can compensate for an age-related decline in NO˙-mediated vasodilation. In particular, clinical studies have only Selleck HM781-36B begun to consider two important possibilities regarding the role of ROS in the loss and/or maintenance of endothelium-dependent vasodilatation that occurs with advancing age. Delp and colleagues explore the possibilities that tight regulation of the balance of ROS is more critical to preservation of endothelium-dependent function in the aged vasculature than the absolute levels of any specific molecule or enzyme and/or ROS act as
vasodilatory signaling molecules that compensate for an age-induced reduction in NO˙ signaling. However, while numerous studies have implicated a role for H2O2 in regulation of vascular resistance in humans and some such as that by Henriksson et al. [4] in this volume of Microcirculation not demonstrated a role for ROS in the skin, little is known regarding the effects of age on ROS signaling in the microcirculation
of humans in key organs such as peripheral muscle and the myocardium. One way to study the coronary microvasculature in vivo in humans is by studying refractory angina. Refractory angina is normally observed in patients with CAD who do not respond to anti-angina treatment such as nitrates. There are multiple mechanisms that could explain this nitrate intolerance and while it is assumed that, in some patients, adding extrinsic NO˙ to an oxidatively stressed microvasculature would increase ONOO˙− production resulting in a further decrease of NO˙ bioavailability, in the elderly patient’, adding extrinsic NO˙ could disrupt the “new” vascular redox status, limiting ONOO˙− as an NO˙ donor. Currently, these hypotheses are speculative, and there is ample opportunity for new studies investigating the role of NO˙ and ONOO˙− in the coronary and other microcirculatory beds both in healthy aging and in elderly patients where the effectiveness of therapeutic interventions relies upon comprehensive knowledge of the alterations in vascular control mechanisms that occur with advancing age.