Local Control of Blood Pressure

Question 1

Blood flow to different regions

• During rest
• During non-rest

Answer 1

• During rest
  
  • Total cardiac output = 6 L/min
  • All tissues receive substantial perfusion
  • Some vasoconstriction occurs because baseline SNS activity binds to alpha receptors on vascular smooth muscle
    
    • Administration of a ganglionic blocker (ex. hexamethonium, a nicotonic receptor antagonist) decreases BP
  • Some vasodil​ation occurs b/c smooth muscle (heart, skeletal muscles, liver) bind beta2 receptors
    
    • Increases blood flow to heart, skeletal muscles, & liver
    • beta2 receptors have a higher affinity for Epi than NE
    • Vasodilation occurs in response to Epi release
  1. Some vasodilation occurs in the penis & clitoris during sexual excitement b/c sacral PNS neurons release nitric oxide
• During non-rest
  
  • Total cardiac output increases
  • Blood flow increases to some parts of the body & diminishes to others
  • Myogenic autoregulation: controls peripheral resistance by allowing vascular smooth muscle to regulate its own activity
    
    • Influenced by release of paracrines: chemicals secreted by cells that affect contraction of nearby vascular muscle
    • Also influenced by hormones

Question 2

Myogenic Autoregulation

Answer 2

• Blood vessels adjust their diameter in response to alterations in BP so flow through the vascular bed remains constant
  
  • Flow & perfusion pressure are directly proportional
  • Vascular resistance increases proportionally to an increase in pressure
• Occurs in denervated vessels
  
  • Neural influences aren’t needed to produce this effect
  • All vascular beds autoregulate
• Increased pressure –> vascular smooth muscle cell walls stretch –> open stretch-sensitive Na+ channels –> depolarization –> open voltage-gated Ca2+ channels –> increase [Ca2+]_i –> vasoconstriction
  
  • Increased pressure –> initial distension of arteriolar wall is a stimulus for activation of smooth muscle cells –> vessel diameter decreases
• Autoregulation provides a constant rate of O2 delivery regardless of perfusion pressure

Question 3

Local control of vascular resistance

• Accumulation of chemicals during exercise
• Adenosine & K+
• Additional paracrine factors

Answer 3

• Accumulation of chemcials during exercise –> increased skeletal muscle perfusion
  
  • Release of metabolites (H+ from acids, K+, CO2) –> vasodilation
  • Low O2 levels –> vasodilation
    
    • Mediated by release of adenosine from muscle cells during hypoxia
• Adenosine & K+: metabolites w/ the strongest effects on vasoconstriction
  
  • Increase adenosine –> increase cAMP –> activate protein kinase A (PKA) –> phosphorylate & open K-ATP channels –> K+ efflux –> hyperpolarization
  • Increase [K+]_o –> increase conductance through K-IR channel –> hyperpolarization
  • Increase metabolism –> increase [K+]_o –> open & increase K+ conductance throug hK-IR channels –> hyperpolarization –> close voltage-gated Ca2+ channels –> smooth muscle relaxation / vasodilation
• Additional paracrine factors regulate blood flow to particular vascular beds
  
  • Endothelin: released from damaged endothelial cells –> vasoconstriction –> reduce bleeding from damaged arteries
  • Serotonin: released from activated platelets –> vasoconstriction –> prevent blood loss
  • Histamine: released from healing tissues on mast cells –> vasodilation

Question 4

Endothelium-derived relaxing factor

• EDRF
• Sheer stress
• Additional mechanotransduction mechanism

Answer 4

• Endothelium-derived relaxing factor (EDRF): substance in endothelial cells that relaxes blood vessels –> vasodilation
  
  • Chemical agents (Ach, bradykinin, ATP) & blood flow –> NO production
• Sheer stress: produced by blood flowing across the surface of endothelial cells
  
  • Opens mechanically-gated channels on the surface
  • Ca2+ enters endothelial cells
  • Ca2+ combines w/ calmodulin (CM)
  • Ca2+-CM complex activates NO synthase
• Additional mechanotransduction mechanism
  
  • Initiates a kinase cascade
  • Phosphorylation of NO synthase
  • Activation of NO synthase
  • Increased NO production

Question 5

Nitric Oxide

• NO after synthesis
• Other ways NO is released/synthesized (besides sheer stress)

Answer 5

• NO after synthesis
  
  • Diffuses from endothelial cells to adjacent smooth muscle cells
  • Activates guanylate cyclase
  • Increases cGMP
  • activates ATPase to pump Ca2+ out of smooth muscle cells
  • Inhibits actin-myosin interactions
  • Relaxes smooth muscle –> vasodilation
• NO released when endothelial cells are exposed to bradykinin
  
  • Bradykinin released during cellular damage
• Products of metabolism –> vasodilation –> NO synthesis

Question 6

Parasympathetic production of NO & Viagra

Answer 6

• PNS innervation of a limited number of vascular beds (i.e., genitalia) produces NO
  
  • NO release in the male corpus cavernosum –> NO release –> erection
• Viagra (sildenafil) enhances effect of NO
  
  • Inhibits Phosphodiesterase type 5 (PDE5) for degradation of cGMP
  • Increases cGMP levels
  • Smooth muscle relaxes / vasodilates
  • Blood flows to the corpus cavernosum
  • No effect in the absense of sexual stimulation

Question 7

Role of erythrocytes in regulating blood flow

Answer 7

• Release of oxygen & vasodilator substances form erythrocytes are coupled
  
  • Increase O2 release –> areriole vasodilation –> tissues utilizing a lot of O2 will receive increased blood flow
• NO is continuously produced by endothelial cells
  
  • NO reacts w/ O2 to form the nitrate NO2-
  • Deoxygenated hemoglobin function as a NO2- reductase to regenerate NO from NO2-
  • Erythrocytes produce NO –> O2 dissociates from hemoglobin
• ATP
  
  • Produced in the erythrocyte by glycolysis
  • Released in response to off-loading of O2
  • Triggers the release of NO from endothelial cells
• Off-loading of O2 from erythrocytes
  
  • –> local vasodilation
  • –> delivery of more erythrocytes to the area utilizing O2
  • During exercise, this mechanism enhances O2 delivery to working muscles

Question 8

Coronary / Cardiac Muscle Circulation

Answer 8

• Coronray arteries branch from the aorta to perfuse the heart
  
  • Only ~100 micro-m of the inner endocardial surface can obtain significant amounts of nutrition directly from the blood supply in the cardiac chambers
• Blood flwo through coronary capillaries during diastole > systole
  
  • During ventricular contraciton, blood flows throught the capillaries is obstructed by compression of the vessels
  • Blood flow increases during diastole when the muscle around the vessels relaxes
• Autoregulatory mechanisms adjust blood flow through the heart
• Epi released from adrenal glands also influences coronary artery dilation

Question 9

Cerebral Circulatoin

Answer 9

• Almost completely insensitive to neural & hormonal influences that produce vasoconstriction elsewhere in the body
• Paracrine release: predominant factor that controls blood flwo through the cerebral circulation
• Carbon dioxide: strong vasodilation effect

Question 10

Skeletal Muscle Circulation

• Similarities to cardiac circulation
• Differences from cardiac circulation

Answer 10

• Similarities to cardiac circulation
  
  • Paracrine factors have strong influence
  • Epi released from teh adrenal glands –> vasodilation
• Differences from cardiac circulation
  
  • Skeletal muscle arterioles are richly innervated by SNS vasoconstrictor fibers
    
    • Major resistance vessels that contribute to total peripheral resistance
  • Skeletal muscle mass is larger
    
    • Vasodilatoin of muscle vessels would greatly diminish total peripheral resistance unless vasoconstriction occurs in other vascular beds

Question 11

GI Tract Circulation

• Paracrine factors
• Activity in the GI tract during digestion
• Postprandial hypotension

Answer 11

• Paracrine factors influence splanchnic circulation
  
  • Long-chain fatty acids that are being absorbed & hormonal agents that influence digestion –> dilation
• Activity in the GI tract during digestion (secretion / motility)
  
  • Increase gut blood flow
• Postprandial hypotension
  
  • Ex. when stand up from dinner table
  • Gut arterioles are innervated by SNS efferents
  • Blood flow to the GI tract decreases during exercise or when blood is needed elsewhere

Question 12

Cutaneous Circulation

• General
• Temperature
• Bradykinin

Answer 12

• Skin requires little blood flow
• Temperature
  
  • High temperature –> SNS efferents stop firing –> increase blood flow –> cooling
  • Low temperature –> SNS efferents fire –> decrease blood flow
• Bradykinin release during sweating –> vasodilation
  
  • Release of NO from endothelial cells –> increase blood flow –> cooling

Question 13

The Fick Principle

Answer 13

• Fick Principle
  
  • Estimates blood flow to different organs
  • Delivery of oxygen to a tissue = difference b/n concentration of that substance in arterial & venous blood
  • Determines pulmonary blood flow / cardiac output
• Equations
  
  • CaO2 = arterial O2 content
  • CvO2 = venous O2 content
  • F = blood flow
  • Rate of O2 delivery = F * CaO2
  • Rate of O2 removal = F * CvO2
  • Oxygen delivery = QO2 = F * (CaO2 - CvO2)
  • F = QO2 / (CaO2 - CvO2)
• Applying Fick Principle to determine oxygen consumption in different vascular beds
  
  • Organs that are very metabolically active (heart, skeletal muscle)
    
    • CaO2 - CvO2 (oxygen consumption) is high
    • F (blood flow) is low
  • Vascular beds that receive substantial blood flow for purposes other than to meet metabolic needs (skin, kidneys)
    
    • CaO2 - CvO2 (oxygen consumption) is low
    • F (blood flow) is high