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03/06/02 1
K 305
2 June 03
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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)
03/06/02 13
Vascular Smooth Muscle Cells
• Endothelium
• Neural
• Other Tissues
• Intrinsic Factors
Regulation of Flow (Q)
03/06/02 14
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)
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