Sustained Post-exercise Vasodilation: Histaminergic Mechanisms and Adaptations
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Blood flow to the previously active skeletal muscle remains elevated for several hours following an acute bout of aerobic exercise and is dependent on activation of H1 and H2 histamine receptors. Many questions remain unanswered in humans regarding the mechanisms mediating this sustained post-exercise vasodilation and what benefits come of this physiological phenomenon. The studies detailed in this dissertation were designed to examine the upstream mechanisms and explore a potential benefit associated with sustained post-exercise vasodilation. In chapter IV, we examined if oxidative stress is the upstream exercise-related factor mediating sustained post-exercise vasodilation. Intravenously infusing the antioxidant ascorbate blunted sustained post-exercise vasodilation, and this reduction was similar in magnitude to that observed with H1/H2 blockade. However, ascorbate may directly degrade histamine and may also inhibit its formation. Therefore, we conducted a follow-up study to verify the findings in study 1. In this study, we intravenously infused n-acetylcysteine, a potent antioxidant with no known histaminergic interactions. We found that n-acetylcysteine had no effect on sustained post-exercise vasodilation, indicating that exercise-induced oxidative stress is not the exercise related factor mediating sustained post-exercise vasodilation. In chapter V, we attempted to measure interstitial histamine in an effort to demonstrate that exercise induces the local formation of histamine in previously active skeletal muscle. We found that histamine is increased in the interstitial fluid within skeletal muscle during and after exercise. Additionally, we determined that de novo synthesis via histidine decarboxylase contributes to the rise in histamine during and following exercise. We also demonstrated a possible role of mast cells as an additional mechanism augmenting histamine in skeletal muscle. Collectively, these studies demonstrate that histamine is the ligand activating histamine receptors and activation is due to the induction of histidine decarboxylase and mast cell activation. In chapter VI, we attempted to determine if histamine receptor activation contributes to the expression of pro- and anti-angiogenic growth factors during the recovery from exercise. Our preliminary findings indicate that activation of histamine receptors may play a role in the expression of pro-angiogenic growth factors during the recovery from acute aerobic exercise.