Vascular Control - Nordgren

Question 1

What are the major ways in which smooth muscle differs anatomically and functionally from striated muscle?

Answer 1

1. Contract/relax more slowly
2. Contractile activity as result of either AP or RMP
3. Can change contractile activity in absence of any changes in membrane potential
4. Can maintain tension for prolonged periods at low energy cost
5. Can be activated by stretch

Question 2

What are the steps leading to contraction in vascular smooth muscle?

Answer 2

1. Ca²⁺ complexes with calmodulin
2. This complex activates myosin light-chain kinase (MLCK)
3. MLC kinase allows ATP to phosphorylate MLC protein
4. MLC phosphorylation enables cross-bridge formation & cycling, during which energy from ATP is utilized for tension development/shortening

***VSM contractility depends on the NET state of MLC phosphorylation!

Question 3

What are the steps leading to relaxation in vascular smooth muscle (after contraction)?

Answer 3

1. Myosin phosphatase facilitates reaction involving MLC-PO₄
2. Removal of phosphate from MLC returns cell to relaxation

Question 4

How does Electromechanical coupling occur in the vascular smooth muscle?

Answer 4

• Membrane depolarization opens Voltage Operated Ca²⁺ Channels (VOC) →
  
  • Ca²⁺ in → contraction
• Membrane hyperpolarization leads to smooth muscle relaxation
• VOCs are partially activated at low RMP of the vascular smooth muscle
  
  • alterations to RMP can alter basal contractile state

Question 5

How does Pharmacomechanical Coupling occur in the vascular smooth muscle?

Answer 5

• Pharmacologic substance binds to G-protein coupled receptor
• GTP-binding proteins initiate opening of Receptor Operated Ca²⁺ Channels (ROC)
  
  • Ca²⁺ in → contraction

OR

• GTP-binding proteins initiate PLC to use PIP₂ to convert into DAG & IP₃
  
  • formation of IP₃ opens Ca²⁺ channels on sarcoplasmic reticulum
  • Ca²⁺ increases → contraction

Question 6

What is basal tone?

Answer 6

Arteriole remains in a state of partial constriction, even after removal of all external influences.

Question 7

What substances are potentially involved in local metabolic control?

Answer 7

• Metabolic
  
  • low O₂, high CO₂/H⁺/K⁺, release of Adenosine
• Endothelial cells
  
  • produce Nitric Oxide (relax smooth muscle)
• Other chemicals
  
  • Prostaglandins & Thromboxane
  • Leukotrienes, Histamine, Bradykinin
• Transmural pressure
  
  • slight passive distencsion activates VSM constriction that then reverses the initial distension

Question 8

How is vascular tone influenced by endothelia, prostaglandins, histamine, and bradykinin?

Answer 8

• Endothelia produce NO → VSM relax
  
  • NO stimulates cGMP production → cGMP inhibits Ca²⁺ entry
  • NO activates MLC phosphatase, K⁺ channels → hyperpolarization
• Prostaglandins, Histamine, Bradykinin
  
  • some are vasodilators, others are vasoconstrictors
  • ones produced by endothelial cells are vasoconstrictors

Question 9

What is the myogenic response of blood vessels?

Answer 9

AKA: Active Phase of Transmural Pressure

• Arterioles are actively and passively responding to changes in transmural pressure
  
  • in order to keep blood flow constant
  • a sudden decrease in transmural pressure triggers the opposite response
  • due to activation of stretch-sensitive ion channels on arteriolar VSM cells

Question 10

What is active and reactive hyperemia?

Answer 10

• Active Hyperemia:
  
  • in organs with highly variable metabolic rate, the blood flow closely follows the tissue’s metabolic rate
  • e.g. Skeletal, cardiac
• Reactive Hyperemia:
  
  • higher than normal blood flow after removal of restriction
  • duration dependent on severity of occlusion and metabolic needs
  • e.g. tourniquet

Question 11

Define autoregulation of blood flow.

Answer 11

• Despite variations in arterial pressure, nearly all organs tend to keep their blood flow constant
  
  • think of kinked water hose:
    
    • no matter how many twists, kinks, or high the water is turned up, the vessels accomodate the changes to maintain a constant flow despite pressure changes

Question 12

What is neurogenic tone of vascular muscle?

Answer 12

• when tone is increased above basal levels due to continual firing (tonic firing) activity
  
  • caused by a release of NE in proportion to AP frequency
    
    • NE combines with alpha-1 adrenergic receptors on smooth muscle cells
    • increased nerve activity = increased vasoconstriction
  • sympathetic vasoconstrictor nerves innervate arterioles in all systemic organs

Question 13

How is vascular tone influenced by circulating catecholamines, vasopressin, and angiotensin II?

Answer 13

• Interact with specific receptors:
  
  • alpha-1 adrenergic
    
    • lots in vasculature
    • vasoconstriction (e.g. Angiotensin II)
  • beta-2 adrenergic
    
    • only in arterioles of some organs
    • vasodilation (e.g. Vasopressin/ADH)

Question 14

What are the major influences on venous diameters?

Answer 14

• external compressional forces (e.g. skeletal muscle)
  
  • most important
• internal pressure
• sympathetic nerves (NE → alpha-1 adrenergic)
  
  • vasoconstriction
  • have little effect on veins becaus of normal dilated state and little basal tone

Question 15

What is the relative importance of local metabolic and neural control of coronary blood flow?

Answer 15

• Local metabolic:
  
  • Coronary blood flow is controlled primarily by local metabolic mechanisms
• Neural Control:
  
  • sympathetic vasoconstrictor nerves do not appear to influence coronary flow enough to affect the mechanical performance of normal hearts.

Question 16

What is systolic compression?

Answer 16

• Large forces and/or pressures generated within the myocardial tissue during cardiac muscle contraction press on the outside of coronary vessels and cause them to collapse during systole

Question 17

What is its relative importance to blood flow in the endocardial and epicardial regions of the right and left ventricular walls?

Answer 17

• left ventricular myocardium = coronary flow is lower during systole than during diastole, even though systemic arterial pressure (ie, coronary perfusion pressure) is highest during systole
• Systolic compression has much less effect on flow through the right ventricular myocardium
• Systolic compressional forces on coronary vessels are greater in the endocardial (inside) layers of the left ventricular wall than in the epicardial layers.
  
  • Thus, the flow to the endocardial layers of the left ventricle is impeded more than the flow to the epicardial layers by systolic compression.

Question 18

What are the major mechanisms of flow and blood volume control in skeletal muscle?

Answer 18

• Flow:
  
  • Local metabolic control of arteriolar tone is the most important
  • muscle oxygen consumption is the most important determinant of its blood flow
  • less important is sympathetic neural activity
• Blood volume control:
  
  • Rhythmic contractions

Question 19

What are the major mechanisms of flow and blood volume control in the brain?

Answer 19

• Flow:
  
  • Cerebral blood flow is regulated almost entirely by local mechanisms
  • Local changes in cerebral blood flow may be influenced by local metabolic conditions
    
    • H+, K+, oxygen, and adenosine seem most likely to be involved
  • Cerebral blood flow decreases whenever arterial blood PCO2 falls below normal.
  • Sympathetic and parasympathetic neural influences on cerebral blood flow are minimal.
• Blood volume control:
  
  • autoregulation
  • BBB

Question 20

What are the major mechanisms of flow and blood volume control in the splanchnic organs?

Answer 20

• Flow:
  
  • Sympathetic neural activity plays an important role in vascular control of the splanchnic circulation
  • Local metabolic activity associated with gastrointestinal motility, secretion, and absorption is associated with local increases in splanchnic blood flow
• Blood volume control:
  
  • a large fraction of the blood mobilized from the splanchnic circulation during periods of sympathetic activation comes from the constriction of veins in the liver

Question 21

What are the major mechanisms of flow and blood volume control in the kidneys?

Answer 21

• Flow:
  
  • Renal blood flow is strongly influenced by sympathetic neural stimulation.
  • Local metabolic mechanism may influence local vascular tone, but physiological roles are not clear.
• Blood volume control:
  
  • The kidneys normally receive approximately 20% of the cardiac output of a resting individual.
  • This flow can be reduced to practically zero during strong sympathetic activation.

Question 22

What are the major mechanisms of flow and blood volume control in the skin?

Answer 22

• Decreases in body temperature decrease skin blood flow and vice versa.
• Cutaneous blood flow, which is approximately 6% of resting cardiac output
  
  • can decrease to about one-twentieth of its normal value when heat is to be retained (eg, in a cold environment, during the development stages of a fever). In contrast, cutaneous blood flow can increase up to seven times its normal value when heat is to be lost

Question 23

Why is the mean pulmonary arterial pressure lower than mean systemic arterial pressure?

Answer 23

pulmonary vascular resistance is inherently much lower than systemic total peripheral resistance

The pulmonary bed has a low resistance because it has relatively large vessels throughout

Question 24

How is pulmonary vascular control different from that in systemic organs?

Answer 24

• Autonomic nerves play no major role in control of pulmonary vascular activity.
• Both pulmonary arteries and veins receive sympathetic vasoconstrictor fiber innervation, but reflex influences on pulmonary vessels appear to be much less important than the physical and local hypoxic influences