This dissertation, written by Sridevi Nagaraja, and entitled Theoretical investigations of intercellular communication in the microcirculation: conducted responses, myoendothelial projections and endothelium derived hyperpolarizing factor, having been approved in respect to style and intellectual content, is referred to you for judgment.We have read this dissertation and recommend that it be approved.
_______________________________________Wei-Chiang Lin dynamics in vascular cells in single as well as multicellular models. Advancement of these models is necessary to achieve the level of sophistication analogous to cardiac models. These models will contribute towards the development of a theoretical framework for the understanding of microcirculatory phenomena. It is also one of the most thoroughly studied vascular beds with vast amount of experimental data available. Therefore, in most of our models we use data from small rat mesenteric arteries (RMAs). This section describes the major channels and pumps present within the cytosol in the longitudinal direction of the cell.Through this process, it has become obvious that detailed models of Ca is still a need to build upon previous modeling work in order to develop cellular models that will assist in the investigations of vascular tone regulation in health and disease. Other channels specific to EC are described below.
Inward rectifier potassium channelsInward rectifier potassium channels (K ir ) are sensitive to extracellular concentration of potassium in the range of 1 to 20 mM. These channels increase entry of potassium into the cell thereby hyperpolarizing of EC and subsequently the SMC. They are present in almost all endothelial cells and contribute towards the resting V m of the EC. EC K ir channels are known to be activated not only by potassium but also by shear stress.
Theoretical modeling of vascular ECsThe first endothelial cell models were based on earlier generic models of Ca
Endothelium derived controllers
Nitric oxideNitric oxide was identified as the endothelium derived relaxing factor in 1980
ProstacyclinProstacyclin (PGI2) in rat mesenteric arterioles, PGI2 does not exert a hyperpolarizing effect. The involvement of PGI2 pathways is usually studied using COX inhibitor (Indomethacin).
Endothelium derived hyperpolarizing factorEDHF is an endothelium derived non-nitric oxide (NO) and non-cyclicoxygenase and EC hyperpolarization by activation of IK Ca and SK Ca is now a widely accepted finger print of EDHF action across many studies.However, its propagation to the SMC is still being investigated.
Myoendothelial feedbackStudies have shown that endothelium derived pathways can also be induced during SMC stimulation which brought about the concept of myoendothelial feedback. where R gj is gap junction resistance, and ∆V gj represents V m cells n-th and m-th ( Figure 2.2). where P gj,S is the gap junction permeability to S (e.g., Ca rectification is low at physiological concentration gradients, and a simpler linear approximation can ...