Nitric Oxide Flashcards
EDRF
What Nitric Oxide was first identified as
Vasodilation when activated by Ach, Bradykinin, Histamine, ATP
NOS (Role in L-Arginine-NO Pathway)
Nitric Oxide Synthase
Activated by Ca2+
Activated by Mechanical Shear Stress
Converts Arginine and Oxygen into NO
NO (Role in L-Arginine-NO Pathway)
Activates Soluble Guanylyl Cyclase which activates guanylyl cyclase in Smooth Muscle Cells
GC (Role in L-Arginine-NO Pathway)
Guanylyl Cyclase
Converts GTP into cGMP
cGMP (Role in L-Arginine-NO Pathway)
Causes Relaxation
PDE5
Terminates cGMP signal by converting it into 5’GMP
eNOS
Vascular Effects of Endothelial NO
NO causes:
Platelet Inhibition
NO activates sGC activating cGMP downstream –> Relaxation
Decrease Blood Pressure
Decrease Vascular Resistance
nNOS
Neuronal Effects of NMDA NO
Activation of NMDA generates NO
CNS = Neurotransmitter
Learning and Memory
PNS = NANC Neurotransmitter
Neurogenic Vasodilation
Relaxation: GI, resp, genitial, Urinary
Neuroendocrine
Reproduction
Aggression
Feeding
iNOS
Defense Mechanism Effects of NO
Has Calcium/Calmodulin already bounded
Regulated at transcription
Expressed in response to bacteria endotoxin
Glucocorticoids
Inhibit iNOS Expression
Glyceryl Trinitrate (Nitroglycerin)
NO Donor
Activates sGC in smooth muscle cells
Converts GTP into cGMP
cGMP signals downstream
Phosphorylating Protein Kinases
Causing Relaxation
Nitroprusside
NO Donor
Activates sGC in smooth muscle cells
Converts GTP into cGMP
cGMP signals downstream
Phosphorylating Protein Kinases
Causing Relaxation
Statins
Lowers Cholesterol
Increase NO
Activates sGC –> Activates cGMP downstream
–> Relaxation
Slidenafil
Inhibits PDE5
More cGMP that can signal downstream
Tadalafil
Inhibits PDE5
More cGMP that can signal downstream
