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K 305 2 June 03. Regulation of Flow (Q). Vascular Smooth Muscle Cells Endothelium Neural Other Tissues Intrinsic Factors. Regulation of Flow (Q). Vascular Smooth Muscle Cells Endothelium Neural Other Tissues Intrinsic Factors. Regulation of Flow (Q). Vascular Smooth Muscle Cells - PowerPoint PPT Presentation
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03/06/02 1
K 305
2 June 03
03/06/02 2
03/06/02 3
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Vascular Smooth Muscle Cells
• Endothelium
• Neural
• Other Tissues
• Intrinsic Factors
Regulation of Flow (Q)
03/06/02 5
Vascular Smooth Muscle Cells
• Endothelium
• Neural
• Other Tissues
• Intrinsic Factors
Regulation of Flow (Q)
03/06/02 6
Vascular Smooth Muscle Cells
• Endothelium
• Nitric Oxide
• Endothelin
• EDRF
Regulation of Flow (Q)
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Nitric Oxide•NO (EDRF) synthesized in endothelial cells by NOS
•NOS stimulated by elevated [Ca2+]i
•NOS converts arginine to NO
•NO freely permeates out of endothelial cell into VSM
•In VSM stimulates guanylyl cyclase increasing cGMP
• cGMP activates PKG which stimulates:
•SERCA (through phospholamban) and PMCA
• Reduces [Ca2+]i - relaxation - VASODILATION
• vasodilator drugs nitroglycerin and nitroprusside
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Nitric Oxide – Ca2+ independent•Activates GC in VSM to stimulate PKG
•PKG prevents Rho A from being activated
•Prevents inhibition of MLC Phosphatase
•Dephosporylates MLK
•Induces relaxation in VSM - VASODILATION
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Vascular Smooth Muscle Contraction
Receptor Activation
Ca2+/calmodulin
MLCK (active)
MLC (contracted)
MLC (relaxed)
P
IP3 PKC
myosin phosphatase (active)
phospholipase C/ heterotrimeric G-protein
Rho-kinase
myosin phosphatase (inactive)
ATP
• Ca2+ dependent activation Ca2+/calmodulin activation of MLCK • Ca2+ independent activation Inhibition of myosin phosphatase by Rho-kinase
(small G-protein)RhoA GDP
RhoA GTPGTP
P
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RhoA-GDP (inactive)RhoA-GTP
(active)
guanylate cyclase
cGMPcG-kinase
Vascular smooth muscle cell
Endothelial cell
xanthine oxidaseNADPH oxidaseuncoupled eNOS
Rho-kinase ATP
contraction
Superoxide activates RhoA
Nitric oxide inhibits the migration of RhoA
O2
NO
relaxation
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Vascular Smooth Muscle Cells
• Endothelium
• Nitric Oxide
• Endothelin
• EDRF
Regulation of Flow (Q)
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Vascular Smooth Muscle Cells
• Endothelium
• Neural
• Other Tissues
• Intrinsic Factors
Regulation of Flow (Q)
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Vascular Smooth Muscle Cells• Neural
• NA – adrenergic receptor
• NA – adrenergic receptor
• ACh – muscarinic receptor
Regulation of Flow (Q)
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Vascular Smooth Muscle Cells
• Endothelium
• Neural
• Other Tissues
• Intrinsic Factors
Regulation of Flow (Q)
