Vascular Endothelium & NO (Caroline)

Vascular Endothelium & NO (Caroline) - Vascular...

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Vascular tone is sum of simultaneous dilating and constictor effects What is going on in vessel-sum of neuronal and hormonal inputs=tone Shear stress, histamine, Ach, Bradykinin, Purigenics activates NO production Vasopressin influences amount of volume that is circulating Epi depending on receptors, cause constriction or dilation Consider complicated system change=feedback that tries to return system to normal. Drugs try to alter this. Some hormones simultaneously produce dilation via enhancing NO production and constriction via direct effects on smooth muscle Direct vs indirect effects Endothelial=important hormone receptors; Make a lot of NO; use a lot of O2; metabolically active! We learned w/ experiments lacking endothelial cells o Nature 1980 Discovery of EDRF Strips of vascular muscle add something to constrict (NE at alpha receptors) and something to relax them. Wash out and do again and again. NE at alpha 1 on smooth muscle causes constriction Gq mobilization of Ca contraction in any kind of muscle Added Ach=no relaxation. Some muscles he got contraction. Added less NE=partial contraction. Cuz tech rubbed away intimal lining=endothelial cells. In absense of ento, relaxant hormone Ach does not cause relaxation but contraction. Therefore, endothelium producing endothelium relaxant factor, later identified as NO. Classical experiment Took organ back of intact intimal lining and added Ach transferred fluid to other cells blocked off cholinergic receptor and still got relaxation=EDRF=NO Endothelial cell produces NO in response to certain hormones NO Diffusible messenger, made by endo cells, made on demand via Gq-PLC-Ca-CaM activation of NOS (isoforms 1 and 3) Endothelial cell has many specializations
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Vascular Endothelium & NO (Caroline) - Vascular...

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