Circulation: Vascular Smooth Muscle

Question 1

What is Vascular tone?

What controls vascular tone?

What regulates vascular tone?

Answer 1

• The amount of vessel constriction RELATIVE TO ITS MAXIMUM DILATION.
• The contractile state of VSM cells - found in all vessels, except capillaries.
• The SNS, PNS, Platelets, Immune cells, Hormones, Metabolic factors.

Question 2

Why do we have intrinsic and extrinsic control of vascular tone?

What are the different extrinsic controls used?

Answer 2

• Intrinsic controls regulate local blood flow to organs/tissues.
  Extrinsic control regulates TPR to control BP, which drives blood flow.

Brain function selectivity alters blood flow to organs according to need.

• Nerves:
  • Vasoconstrictors - NA
  • Vasodilators - ACh, NO

Hormones
• Vasoconstrictor - Adr, Ang II, ADH
• Vasodilators - ANP

Question 3

Describe the stages in the sympathetic vasoconstrictor system

LOOK AT DIAGRAM!

Answer 3

1. Main excitatory drive is from the brainstem (RVLM), which goes to the thoracic spinal cord.
2. Pre-ganglionic sympathetic fibres go to ganglia and adrenal medulla to release ACh.
3. Post-ganglionics release NA at β1-receptors on heart and α1 & β2 receptors on blood vessels. The adrenal medulla releases Adr at α1 & β2 receptors on blood vessels.
4. These all result in vasoconstriction and ↑HR.

Question 4

What are varicosities?

What happens when an action potential reaches this Varicosity?

LOOK AT PICTURE!

Answer 4

• Specialised synapses of vasoconstrictor nerves in the t.adventitia of blood vessels (like “beads on a string”) - have vesicular storage of NA.
• Depolarisation = VGCCs open = Ca2+ influx = Exocytosis of NA. The NA will diffuse to the local VSMCs to act mainly on α1 receptors to cause vasoconstriction. It also acts on some α2 and β2 receptors.

Question 5

What are some important points about sympathetics vasoconstrictor nerves?

Answer 5

• Provides central control of blood flow and BP
• NA activates α1-receptors on VSMCs = Vasoconstriction
• Sympathetic activity is TONIC (1 AP every second) - sets vascular tone. Therefore, ↓Sympathetic activity = Vasodilation.

Question 6

What are the 5 main roles of sympathetic vasoconstrictor nerves?

Answer 6

• Contracts resistance arterioles: Allows vasodilation to occur to ↑blood flow.
• Sympathetic pathways innervate different tissues: Can switch them on for vasoconstriction or switch off for vasodilation. Blood flow can be directed to most demanding body parts.
• Pre-capillary vasoconstriction: ↓Capillary pressure = ↓Filtration and ↑Absorption to maintain blood volume - useful during hypovolemia.
• Controls TPR: maintains arterial BP/flow to brain and heart - pArterial = CO x TPR.
• Controls venous blood reservoir: Venoconstriction = ↓Venous blood volume as more blood is forced towards heart - will ↑SV (via Starling’s)

Question 7

What are the roles of hormonal vasoconstrictors?

Answer 7

Are used to control blood flow/pressure during activity, and to the essential organs (brain, heart) during haemodynamic crisis (haemorrhage, dehydration).

An excess of these hormones can cause too much vasoconstriction = Hypertension and heart failure.

Question 8

Where is Adrenaline released from? Why?

How does Adrenaline cause vasoconstriction?

Answer 8

• Adrenal medulla - due to sympathetic stimulation

- Act on α1-adenoceptors on VSMCs = Vasoconstriction

Question 9

What is Ang II? How does it cause vasoconstriction?

What are the steps in the RAAS?

LOOK AT DIAGRAM!

Answer 9

• Formed in the RAAS, is a very potent molecule (small amount for large effects). They bind to AT1 receptors on VSMCs = Vasoconstriction.
• 1. ↓Blood flow, ↓Na+, and sympathetics stimulate Renin release from the juxtaglomerular cells.
     
     2. Renin goes to Liver and converts Angiotensinogen → Ang I.
     3. Then, the lungs convert Ang I → Ang II, using ACE (Ang converting enzyme).
     4. Ang II causes central vasoconstriction and it stimulates Aldosterone release from adrenal glands.
     5. Vasoconstriction = ↑TPR. Aldosterone release = ↑Na (+ H2O) reabsorption = ↑Blood volume/CO - ↑CO and TPR = ↑BP.

Question 10

How is ADH release stimulated?

What is the effect of ADH secretion?

LOOK AT DIAGRAM!

Answer 10

• 1. ↑BP detected by arterial baroreceptors (ABR) and left atrial receptors (LAR), which send a signal to the NTS in medulla.
     
     2. NTS then sends an INHIBITORY signal to CVLM (caudal ventrolateral medulla), to turn OFF its pathway.
     3. However, ↓BP won’t cause inhibition of CVLM - CVLM can then stimulate the Magnocellular cells in hypothalamus = ADH release from posterior pituitary.
• In kidneys, it binds to V2 receptors to inserts aquaporin channels into CD = ↑H2O reabsorption = ↑Blood volume = ↑BP. ↑↑↑ADH causes vasoconstriction of vessels.

Question 11

What secretes ANP? What stimulates this release?

How do Atrial Natriuretic Peptides (ANP) work to cause vasodilation?

How does ANP reduce BP?

What is ANP a good biomarker for?

Answer 11

• Specialised atrial myocytes - in response to distension of atria from ↑Filling pressures, which stimulates stretch receptors during distension.
• ANP acts on NP receptors on VSMCs = ↑cGMP pathway = Vasodilation
• 1. Systemic vasodilation - ANP opposes action of vasoconstrictor hormones (NA, Adr, Ang II, ADH, ET-1, TXA2)
     
     2. Dilation of renal AFFERENT arteriole - ↑GFR = ↑Na+ (+H2O) excretion = ↓Blood volume = ↓BP
     3. ↓Release of renin, aldosterone, ADH - ↓RAAS
• Poor heart function/congested circulation e.g. in heart failure.