30. Local factors of cardiovascular regulation

Question 1

What should be mentioned in this topic?

Answer 1

Regulation of Circulation

Intrinsic (local) short term Regulation

Autoregulation by myogenic tone

Endothel related regulation

EDRF: mechanism of action

Acetylcholine

Regulations through metabolites

Intrinsic long term regulation

Hyperemia

Question 2

Regulation of Circulation

Answer 2

Main Task:
– Substance (material) transport to and from the tissues should be insured.

– Prevention of the Collapse of circulation by providing sufficient blood supply to the organs according to the metabolic needs.

I. Local (=Intrinsic)

– short term/long term
– This is regulated by fast, local, auto-regulative processes
– Intensity of perfusion (blood flow) is determined mainly by the oxygen and nutrient demand of the organ

II. Central (=Extrinsic)
– short term/long term
– coordinating redistribution
– Maintaining the optimal working condition of the organs in the long run needs central (extrinsic) regulations provided by central nervous system, CNS/hormones, adjusting the contraction status of arteries and veins (coordinating redistribution).

Question 3

Intrinsic (local) short term Regulation

Answer 3

fast adjustment of perfusion state
1. Autoregulation and myogenic regulation

– Perfusion rate is supposed to be constant!! (blood pressure↑ → metarteliola constricts)

2. Endothel Derived Regulation – EDRF, EDCF
3. Metabolites Related Regulation
   – It is the most important local auto-regulative element

– pO2, pH, pCO2, K+ conc., adenozine…

Question 4

Autoregulation by myogenic tone

Answer 4

Microcirculation should not bee influenced by the changes of peripheral blood pressure.

– Stability must be maintained, which is provided by myogenic adaptation.

• Bayliss effect

– Pressure changes initiate adequate response of metarterioles’ sphincters (contraction or relaxation), so perfusion will adapt to the metabolic demand. So microcirculation works, perfusion is stabile, or it is adjusted to the needs.

Autoregulation of perfusion exists within the range of 40 – 140 mmHg arterial pressure

– pressure increase results in sphincter contraction at metarteriole

– pressure decrease results in sphincter relaxation,

– therefore perfusion pattern will always be adapted to the need – Bayliss

Question 5

Endothel related regulation

Answer 5

§The blood pressure mechanically deforms endothelial cells. This and many plasma cell factors prompt the cells to produce humoral signals that influence the contraction state of smooth muscle in the wall of the vessel itself.

§We have two major classes:

1. EDRF(Endothelial derived relaxing factor): The most important component beside other factors is nitric oxide (a gas) that is continuously produced by the endothelial cells and causes relaxation of smooth muscles (dilation of vessels)
2. EDCF(Endothelial derived constricting factors): Many factors that cause constriction of the smooth muscle of the vessels. The major factors are endothelins.

Question 6

EDRF: mechanism of action

Answer 6

• NO dilates the vessel by triggering relaxation of vascular smooth muscle. The endothelial cells are able to detect high shear stress in the vessel, and release NO as needed to reduce local blood pressure.
• NO is not a hormone, but a short term, local, fast-acting chemical
• Damage to the endothelial cells or to eNOS can reduce the ability for cells to produce NO, leading to stiff vessels, and vascular disease.
• NO can also trigger guanylate cyclase to produce cAMP (cyclic guanin monophosphate), which also acts as a vasodilator

Question 7

EDCF: mechanism of action

Answer 7

Here chemical mediators are released into the smooth muscle by endothelial cells, in order to hyperpolarize them.

• It’s thought that EDHF is actually K+, as when K+ is moved outside the cell, Na+- K+-ATPase is activated, followed by hyperpolarization, and smooth muscle relaxation.
• However, K+ involvement in EDHF mediated relaxation does not always activate Na+- K+-ATPase
• The current theory is that K+ and gap junctions between the cells are simultaneously involved in EDHF relaxation

Question 8

Acetylcholine

Answer 8

-Acetylcholine has different effects on the diameter of vessels depending on the route of application.

It either:

• Liberates from nerve endings of the smooth muscle. This causes contraction
• Injected into the lumen of the vessel. This causes dilation

Question 9

Regulation through metabolites

Answer 9

This is the most important local autoregulative element.

• Mechanism of Action: increased metabolic activity results

in:

– increased O2-consumption (pO2 decreases = hypoxia)

– increased adenozine concentration

– increased H-ion concentration

– increased CO2 concentration

– increased K-ion concentration

• all of these factors stimulate the endothelium (EDRF stimulation).
• Response: NO (nitrogen monoxide) production increases, fast diffusion of NO into the smooth muscles, increasing cGMP: the result is relaxation. PGI2 and hyperpolarizing factors are also released.

Question 10

Intrinsic long term regulation

Answer 10

• When an organ changes its morphology for better perfusion
• This is done by the help of growth factors, enzyme induction and more
• This is increased perfusion by angiogenesis which means the rearrangement and formation of new vessels

Question 11

Hyperemia

Answer 11

• Active hyperaemia changes with the metabolic activity of the tissue. For example when you exercise you have more blood in the vessels
• Reactive hyperaemia is a secondary increase of the perfusion of an organ. This can be due to inflammation or the compression of an artery causes hyperaemia after releasing the pressure