Characterization of vascular endothelial and smooth muscle cell pathways and their contributions to myogenic and agonist‐mediated control (677.16)

Vascular smooth muscle cell contraction and relaxation is central to the local regulation of blood flow to tissue. At the arteriolar level, interactions between vascular endothelial cells and smooth muscel cells play critical role in determining the level of vascular tone. During mechanical and/or agonist stimulations, vascular Ca2+ dynamics are finely adjusted via a number of signaling pathways and the Ca2+ levels in the smooth muscle cells determine the level of contraction. To quantify how cellular Ca2+ dynamics are transformed into changes in vascular tone, we have constructed a cellular‐based model of isolated resistance vessel by integrating models of vessel wall mechanics, smooth muscle force generation, smooth muscle Ca2+ handling and electrophysiology with an endothelial electrophysiology and Ca2+ handling model. The dose‐response vasodilation and vasoconstriction data of different sizes of vessels in response to pharmacological vasoconstrictors and vasodilators, measured using a novel isovolumic myograph developed by Lu and Kassab are analyzed. The model simulates how changes in intraluminal pressure are used to maintain a constant vessel diameter during application of phenylephrine and acetylcholine. In order to simulate these sets of experimental data the model captures integrated vessel behavior including ionic (Ca2+, K+, Na+, etc.), IP3 and nitric oxide myoendothelial transport. Model analysis shows that α‐adrenergic pathways in smooth muscle and NO pathways in endothelium are sufficient to capture the experimentally observed phenylephrine and acetylcholine mediated responses. Grant Funding Source : NIH U01 HL118738, NSF CBET 1133260 and NIH P50‐GM094503