The blood flow to the peripheral circulation is regulated to maintain a balance between the delivery of nutrients and the metabolic demands of the tissue. Blood flow increases to a metabolically active tissue. This increased blood flow is the result of an increase in arteriolar diameter of terminal arterioles and larger upstream vessels. The terminal arterioles appear to determine distribution of flow while the upstream or """"""""feed"""""""" vessels are more important in regulating total tissue flow. With an increase in metabolism there is the release of vasoactive metabolites from the tissue. Although vasoactive metabolites are known to affect the diameters of terminal arterioles the mechanisms by which metabolic factors regulate the diameter of upstream arterioles is uncertain. Recent studies from our lab and others have indicated an important role for the venular-arteriolar diffusion of vasoactive substances. The studies outlined in this proposal will test the following working hypothesis. In response to mismatches in blood flow and tissue metabolism, decreases in PO2 and/or increases in PCO2 and H+ are directly or indirectly sensed by the venular endothelial cells, resulting in the release of vasoactive metabolites of arachidonic acid which regulate the tone of adjacent arterioles. The proposed studies will test this hypothesis utilizing recently developed in situ microcirculatory techniques in which we are able to selectively remove the venular endothelium and assess the impact on blood flow regulation. The proposed studies will test two specific hypotheses: 1) The venular endothelium releases a metabolite of arachidonic acid that diffuses from the venule to the arteriole to cause an arteriolar dilation in response to an increase in tissue metabolic rate. 2) The venular endothelium responds to hypoxia, hypercapnia, and acidosis, directly, or indirectly to initiate the release of one or more vasoactive factors from the venular endothelial cells. These studies should provide new and important information relevant to our understanding the importance of venular-arteriolar diffusion of endothelial derived factors in the regulation of blood flow.
| Naik, Jay S; Xiang, Lusha; Hodnett, Benjamin L et al. (2008) Alpha-adrenoceptor-mediated vasoconstriction is not involved in impaired functional vasodilation in the obese Zucker rat. Clin Exp Pharmacol Physiol 35:611-6 |
| Xiang, Lusha; Naik, Jay S; Hester, Robert L (2008) Functional vasodilation in the rat spinotrapezius muscle: role of nitric oxide, prostanoids and epoxyeicosatrienoic acids. Clin Exp Pharmacol Physiol 35:617-24 |
| Xiang, Lusha; Naik, Jay S; Abram, Sean R et al. (2007) Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane-receptor-mediated vasoconstriction. Am J Physiol Heart Circ Physiol 292:H231-6 |
| Hodnett, Benjamin L; Hester, Robert L (2007) Regulation of muscle blood flow in obesity. Microcirculation 14:273-88 |
| Xiang, Lusha; Naik, Jay S; Hodnett, Benjamin L et al. (2006) Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 290:R134-8 |
| Naik, Jay S; Xiang, Lusha; Hester, Robert L (2006) Enhanced role for RhoA-associated kinase in adrenergic-mediated vasoconstriction in gracilis arteries from obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 290:R154-61 |
| Xiang, Lusha; Naik, Jay; Hester, Robert L (2005) Exercise-induced increase in skeletal muscle vasodilatory responses in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 288:R987-91 |
| Hammer, Leah W; Overstreet, Carmen R; Choi, Jaehwa et al. (2003) ATP stimulates the release of prostacyclin from perfused veins isolated from the hamster hindlimb. Am J Physiol Regul Integr Comp Physiol 285:R193-9 |
| Hester, Robert L; Hammer, Leah W (2002) Venular-arteriolar communication in the regulation of blood flow. Am J Physiol Regul Integr Comp Physiol 282:R1280-5 |
| Hester, Robert L; Choi, Jaehwa (2002) Blood flow control during exercise: role for the venular endothelium? Exerc Sport Sci Rev 30:147-51 |
