Circulation: Endothelium

Question 1

Vasodilator nerves - Sympathetics:
What do they innervate?

What do they release?

What does it lead to?

When will this pathway occur and why?

Answer 1

• Skin
• ACh and VIP
• Sympathetic-mediated sweating
• During exercise, where blood flow needs to be increased for more heat + sweat to be released

Sympathetic vasoconstriction wouldn’t be useful in this scenario as we need more blood reaching skin.

Question 2

Vasodilator nerves - Parasympathetics:
What do they innervate?

What do they release?

What does it lead to?

Answer 2

• Salivary glands, Pancreas/Intestinal Mucosa, Erectile tissue
• ACh/VIP at gland, VIP only at mucosa, NO only at erectile tissue
• ACh/VIP act on endothelium = NO release = Vasodilation. In erectile tissue, NO release = cGMP production = Vasodilation.

Question 3

Vasodilator nerves - Nociceptors::
What stimulates them?

What do they release?

What do they act on?

What does it lead to?

Answer 3

• Trauma, infection
• Sub P and CGRP
• Mast cells, Endothelium, VSMCs
• Histamine release from mast cells and Vasodilation from endothelium and VSMCs.

Question 4

Endothelium-Derived Relaxation Factors (EDRF) - NO release:
What stimulates constant NO release?

What enzyme is used to form NO?

What does it lead to?

LOOK AT DIAGRAM!

Answer 4

• Shear stress from blood flow and inflammatory factors
• eNOS
• It diffuses into VSMCs to activate the GC enzyme = ↑cGMP = ↑PKG = Vasodilation

Question 5

Endothelium-Derived Relaxation Factors (EDRF) - Prostacyclin (PCI2) release:
What stimulates constant PCI2 release?

How is PCI2 produced in the cell?

What does it lead to?

How can COX inhibitors lead to kidney failure?

LOOK AT DIAGRAM!

Answer 5

• Shear stress, inflammatory factors, ACh
• COX enzyme converts membrane lipids into PGI2
• PGI2 leaves and binds to prostanoid receptors on VSMCs = Vasodilation - uses the PKA pathway.
• Reduce production of PCI2 = less renal blood flow = kidney failure.

Question 6

How do the PKA and PKG pathways cause vasodilation?

Answer 6

↑Ca-ATPase (SERCA) = ↑uptake into SR and extrusion from cell. They also ↑K+ channels = Hyperpolarisation = ↓VGCCs. This will then ↓MLCK activity.

*They work to ↓[Ca2+] and Contractility = LESS VASOCONSTRICTION!

Question 7

Endothelium-Derived Hyperpolarisation Factors (EDHF) - K+:
What activates K+ channels?

What does it lead to?

LOOK AT DIAGRAM!

Answer 7

• Shear stress and inflammatory factors
• ↑K+ being pumped OUT = ↑Local external [K+] = Switches on K+ channels and ↑Na/K pump on VSMCs. This will then cause Hyperpolarisation = ↓VGCCs = ↓Ca2+ influx = Vasodilation.

Question 8

Endothelium-Derived Hyperpolarisation (EDH):
What happens when K+ channels are activated?

How does this lead to the hyperpolarisation of the VSMCs?

LOOK AT DIAGRAM!

Answer 8

• K+ efflux = Hyperpolarisation
• Hyperpolarisation is conducted from the endothelium to the VSMC using gap-junctions between the cells. This will then ↓VGCCs = ↓Ca2+ influx = Vasodilation.

Question 9

Explain how stimulation of β2-receptors on VSMCs produces vasodilatation in coronary and skeletal muscle arterioles?

Why is this process important during exercise?

Answer 9

• Stimulation leads to ↑cAMP and PKA, which:
  • ↑SERCA on SR and membrane to ↑Ca2+ uptake and cell extrusion.
  • ↑K+ channel = Hyperpolarisation = ↓VGCCs
  • ↓MLCK
• ↑Blood flow to heart and skeletal muscle

Question 10

What are the other roles of endothelium, apart from regulating vascular tone?

What causes endothelium dysfunction?

Why is endothelial dysfunction linked with CVD?

Answer 10

• • Needed for blood-tissue interactions
  • Ang II production - it contains ACE
  • Blood clotting
  • Inflammation
• Breakdown of epithelium due to Hypertension, Diabetes, Smoking etc.
• It has big effects on vascular tone e.g. ↓NO/PGI2, which will cause lots of vasoconstriction.