Vascular Endothelium & NO (Peace)

Vascular Endothelium & NO (Peace) -...

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04/10/2010 14:57:00 Vascular tone is the sum of simultaneous dilating and constrictor effects Sum of neural inputs Type of receptors expressed determines dilation or constriction Feedback from system works to return system to normal o i.e lower blood pressure, but system returns to high BP Some hormones simultaneously produce dilation (via enhancing endothelial NO  production) and constriction (via direct effects on smooth muscle). How?  NO is a diffusible messenger Made by endothelial cells (among others) o Made on demand via Gq-PLC-Ca++-CaM activation of NOS  Vascular nitric oxide (NO) and the NO synthase pathway and the relationship of  NO to other reactive oxygen species (ROS) NO synthase takes arginine and oxidizes it to citrulline and NO NO binds to heme groups in hemoglobin of RBCs and soluble form of guanyl  cyclase (enzyme that makes cGMP – which causes vasodilation, etc)  o NO + guanylyl cyclase   Increase cGMP   Increase PKG o Consequences of NO generation and cyclic GMP elevation Inhibiton of myosin light chain kinase (MLCK) Activation of myosin light chain phophatase (MLCP) Accelerated Ca++ removal from the cytosol Hyperpolarization of the cell membrane 3 major isoforms of NOS o NOS3 Tissue source: Endothelial cells, CNS, heart o NOS2 Tissue source: Macrophages, smooth muscle cells, liver,  endothelial cells o NOS1
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Tissue: neural cells How smooth muscle works: 
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This note was uploaded on 09/14/2011 for the course PHARM pp taught by Professor Staff during the Spring '11 term at UCSD.

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Vascular Endothelium & NO (Peace) -...

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