Heart failure - Endothelial regulation of vascular tone
13 important questions on Heart failure - Endothelial regulation of vascular tone
What is the function and structure of the aorta and large arteries?
high pressure: "pressure reservoir"
thick-walled, muscular & elastic
-> conducting vessels
What is the function and structure of the small arteries and arterioles?
vascular smooth muscle cells → vasoconstriction & vasodilation/relaxation
--> resistance vessels
What is the function and structure of the capillaries?
very thin-walled, highly permeable (continuous < fenestrated < sinusoid)
--> exchange vessels
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What is the function and structure of the veins and vena cava?
low pressure, high compliance/flexibility: “volume reservoir”
relatively thin-walled, valves assist in unidirectional blood flow back to the heart
--> capacitance vessels
What are the main functions of the endothelium?
- blood pressure control (= regulation of vascular tone) through vasoconstriction & - dilation (hypertension, ischemia)
- prevention of blood loss (= hemostasis) by vascular spasm, platelet aggregation (primary hemostasis) & blood coagulation (secondary hemostasis) (hemophilia, thrombosis)
- inflammation & leukocyte recruitment to (i) promote clearance of dead tissue & wound healing after tissue injury and (ii) elimination of infectious agents & infected cells (atherosclerosis)
- lipid metabolism (atherosclerosis)
- angiogenesis (retinopathy)
How is vascular tone regulated?
- intrinsic (autoregulation) = metabolic control (production of substances) and myogenic (stretch)
- extrinsic = neuronal and hormonal
What are metabolic controls that cause vasodilatation?
-> released into the extracellular space to reach other target cells, but also via gap junctions
What are hormonal controls that cause vasodilation?
What are hormonal controls that cause vasoconstriction?
What is sGC? And what are the domains of this enzyme?
domains:
- N-terminal regulatory or HNOX domain = NO receptor/sensor
- central PAS domain = heterodimerization and signal propagation
- central a-helical/coiled-coil domain = heterodimerization and signal propagation
- C-terminal catalytic domain = TGP -> cGMP
What happens in endothelial dysfunction with oxidative stress?
--> no vasodilatation
What can be used to treat eNOS uncoupling?
Example is nitroglycerin
Besides NO, there are other vasoactive compounds which?
EDCFs: pressure and agonists initiate the production of PGs and ET1
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