Neurotransmission in the vasculature

Question 1

Sensorimotor nerves

Answer 1

Afferent function - picking up information and reflex homeostasis.
Efferent motor function - antidromic vasodilation

Question 2

What are the conditions linked to these nerves?

Answer 2

asthma, eczema, psoriasis and migraines

Question 3

Transmitters used

Answer 3

Substance P and CGRP are stored in the same vesicle and released as cotransmitters.
Other cotransmitters include: ATP, bombesin/gastrin releasing peptide, CCK, dynorphin, galanin, leu-enkephalin, NO, VIP.

Question 4

Capsaicin

Answer 4

Afferent neurons involved in blood flow regulation are sensitive to capsaicin, with low doses causing excitation and high doses causing long lasting damage.
Capsaicin acts at TRPV1 receptors, which are non-selective cation channels.
Persistent depolarisation can cause desensitisation. Capsaicin treatment removes SP and CGRP immunoreactivity, preventing vasorelaxation.
Endocannabinoids and H+ are endogenous TRPV1 ligands. Activating these receptors can lead to the release of substance P.

Question 5

Experiments

Answer 5

Cutting the nerve trunk halfway along its length to separate the endings from the cell body and stimulating below the cut caused a response in the periphery. This suggests that the nerves can convey information in an efferent direction.
Abolishing the dorsal root ganglia abolishes the response, but destroying the sympathetic ganglia does not. This links the sensory nerves to these functions.

Question 6

What are the roles in the cardiovascular system?

Answer 6

Defence against challenges to homeostasis
Vasodilatation and regulation of blood flow
Regulation of cardiac function
Trophic effects
Ageing, hypertension, diabetes

Question 7

Defence against challenges to homeostasis

Answer 7

Sensorimotor nerves are a system of first line of defence against trauma.
Afferent - pain sensation, nocifensive reflexes
Efferent - vasodilation and plasma extravasation as part of neurogenic inflammation

Question 8

Neurogenic inflammation

Answer 8

Sensory nerves cause blood vessels to become leaky in the immune response, causing swelling and redness, e.g. when we are bitten by an insect.
A key component of neurogenic inflammation is hyperemia and increased vascular permeability. This facilitates delivery of leukocytes to tissue, providing resistance against further damage and aiding repair. This is facilitated by CGRP, SP and mast cell histamine.
SP and other tachykinins causes plasma protein extravasation. CGRP facilitates SP-induced increase in permeability.
SP and CGRP have effects on monocytes and macrophages, causing the release of cytokines, prostaglandins, leukotrienes and thromboxanes. These increase vessel diameter, permeability and afferent excitability (sensitization).
In chronic inflammation, sensory motor nerves become hyperactive and contribute to hyperalgesia and perpetuation of the inflammatory response.

Question 9

Blood flow regulation

Answer 9

CGRP is the main molecule controlling dilation, causing potent prolonged vessel dilation. Smooth muscle CGRP receptor activation leads to increased cAMP and opening of K-ATP channels.
SP causes vasodilatation through actions at endothelial NK1 receptors.
NKA causes muscle contraction through actions at smooth muscle NK2 receptors.

Question 10

Evidence for a role of sensorimotor nerves in vasodilatation

Answer 10

When blood vessels are electrically stimulated, vasodilation occurs. Capsaicin abolishes this response, showing that sensory nerves are involved.
Neurogenic relaxation is abolished by capsaicin and blocked by CGRP antagonists. However, it is mimicked by exogenous CGRP.
CGRP levels increase following electrical stimulation, proving that it is released.
Immunohistochemical localisation of CGRP-containing nerves showed evidence of its involvement in sensorimotor vasodilation. SP and VIP innervation was sparse.

Question 11

Regulation of cardiac function

Answer 11

Capsaicin is a potent cardiostimulant. It has positive inotropic and chronotropic effects.
CGRP, SP and NKA are coreleased from cardiac sensorimotor nerves.
CGRP mimics the actions of capsaicin, SP is inactive and NKA opposes the effects.
Cardiac sensorimotor nerves are activated by mediators of inflammation and ischaemia.

Question 12

Trophic effects

Answer 12

Sensorimotor nerves are involved in tissue integrity and wound healing. SP, NKA and CGRP stimulate proliferation of endothelial and smooth muscle cells and skin fibroblasts.
Destruction of sensory nerves reduces skin flap survival.