2 Control of Blood Vessels: Peripheral Resistance

Question 1

Describe peripheral resistance is controlled, by the mechanism of the SNS

Answer 1

All resistance vessels are innervated by the sympathetic nervous system

• when arterial pressure falls, SNS nerve terminals release Noradrenaline onto the VSMC, causing them to contract
• Contraction is mediated by a1-adrenergic receptors acting via the IP3 signalling pathway, causing Ca2+ release from the sarcoplasmic reticulum - CONTRACTION

Question 2

Describe resistance (general)

and what it is determined by

Answer 2

Resistance - directly related to the length of the vessel, the viscosity of fluid and vessel radius
- most important factor is the arteriolar radius
> reduced radius = increased pressure

Arterioles are ‘resistance vessels’

Question 3

Describe what blood vessel radius is dependent on

Answer 3

1. Active tension exerted by smooth muscle (vascular smooth muscle)
2. Passive elastic properties of the wall (elastin and collagen)
3. Blood pressure inside vessel and pressure outside the vessel

Question 4

Describe how sympathetic nerves affect vascular tone

Answer 4

IF a1 or a2 receptors are stimulated:
- there is VASOCONSTRICTION

IF B2 receptors are stimulated
- there is VASODILATION

Question 5

Describe how hormonal control can affect vascular tone

Answer 5

ANP and BNP are released to have a direct vasodilation effect, and reduction in renin

Ang II

• Ang-II binds to angiotensin AT1 receptors on VSMCs
• which couple to the IP3 signalling pathway

ADH
- ADH binds to vasopressin V1a receptors on VSMCs

Adrenaline

• produced in the adrenal medulla
• and released into the blood
• it binds to a-1 adrenergic receptors on the VSMCs to potentiate the SNS-mediated vasoconstriction

Question 6

Describe how prostaglandins are produced

Answer 6

The 2 pain pathways of the arachidonic acid metabolism

• Cyclo-oxygenase (COX) pathways
• Lipoxygenase pathway

Prostaglandins are formed via COX

Question 7

Describe the role that prostaglandins play in the control of vascular control

Answer 7

The endothelium is an important source of a number of vasoactive PGs, which it synthesises from Arachidonic acid

Dilators:

• PGE, PGI2 (prostacyclin)
• they relax the VSMCs in many vascular beds

Constrictors:

• PGF and thromboxane A2
• they are vasoconstrictors
• (PGI2 works in opposition to TXA2)

Question 8

List some chemical mediators that control vasodilation

Answer 8

Vasodilation

• histamine
• nitric oxide (NO)
• Prostacyclin (PGI2)

Question 9

List some chemical mediators that control vasoconstriction

Answer 9

Vasoconstriction

- thromboxane A2 (TXA2)

Question 10

List some chemical mediators that control the increase in venular permeability

Answer 10

Increasing venular permeability

• histamine
• bradykinin
• leukotrienes - LTC4, LTD4, LTE3
• C3a and C5a (complement)

Question 11

List some chemical mediators that control pain production

Answer 11

Producing pain

• PGE2
• Bradykinin

Question 12

List some chemical mediators that control fever production

Answer 12

Producing fever

• PGE2
• IL-1
• TNF (tumour necrosis factor)

Question 13

List some chemical mediators that control chemotaxins

Answer 13

Chemotaxins

• C5a
• LTB4 (for eosinophils - bad for asthma)
• IL-8

Question 14

Describe how Nitric Oxide (NO) can control vascular tone

Answer 14

NO is a potent vasodilator that acts on both arteries and veins

• AKA endothelium-derived relaxing factor (EDRF), it is synthesised by constitutive endothelial NO synthase (eNOS, or NOS3), following a rise in intracellular Ca2+ concentrations
• NO is a gas with a half-life of <10s in vivo, meaning its actions remain highly localised

Nitrates (like GTN for angina) break down to release NO in vivo, causing arterial and venous vasodilation to lower ventricular afterload and preload
- reducing cardiac workload restores the balance between O2 demand and supply and relieves the angina

Question 15

Describe some metabolic factors that can control vascular tone

Answer 15

Cells continuously release various metabolic by-products, including:
- adenosine, lactate, K+, H+, and CO2
(vasodilation)

• Local O2 levels simultaneously fall. Resistance vessels lie close to the cells they serve and are sensitive to the appearance of these metabolites in the extracellular fluid (ECF) and to PO2.
• Some metabolites act directly on VSMCs, whereas others act through endothelial cells, but all-cause the VSMCs to relax and the vessels to dilate.
• Blood flow increases, as a result, simultaneously providing the tissues with the nutrients they need and also carrying away metabolites.
• When activity ceases, metabolite concentrations fall, and reflex vasoconstriction again matches flow with need.

Question 16

Describe which metabolic factors trigger vasodilation

Answer 16

Lactate, H+, K+, and adenosine

increase in these can cause vasodilation

Question 17

Describe the changes that need to happen to O2 and CO2 in systemic vasculature to control vascular tone

Answer 17

Increase in O2 and decrease in CO2
- VASOCONSTRICTION

Decrease in O2 and increase in CO2
- VASODILATION

Question 18

Describe the changes that need to happen to O2 and CO2 in pulmonary vasculature to control vascular tone

Answer 18

Increase in O2 and decrease in CO2
- VASODILATION

Decrease in O2 and increase in CO2
- VASOCONSTRICTION

Question 19

Describe myogenic mechanisms contributing to the autoregulation of blood flow

Answer 19

Autoregulatory range
- where contraction/dilation of VSMCs can affect the arterial range and keep the pressure in this range

Rigid vessels do not have this ability, and there is a complete linear increase in arterial pressure with blood flow

Resistance vessels in many circulations constrict reflexively when intraluminal pressures rise
- Contraction is mediated by stretch-activated Ca2+ channels in the VSMC membranes and may protect capillaries from surges in arterial pressure