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Flashcards in Local Control of Blood Pressure Deck (13):
1

Blood flow to different regions

  • During rest
  • During non-rest

  • 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

2

Myogenic Autoregulation

  • 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

3

Local control of vascular resistance

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

  • 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

4

Endothelium-derived relaxing factor

  • EDRF
  • Sheer stress
  • Additional mechanotransduction mechanism

  • 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

5

Nitric Oxide

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

  • 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

6

Parasympathetic production of NO & Viagra

  • 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

7

Role of erythrocytes in regulating blood flow

  • 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

8

Coronary / Cardiac Muscle Circulation

  • 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

9

Cerebral Circulatoin

  • 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

10

Skeletal Muscle Circulation

  • Similarities to cardiac circulation
  • Differences from cardiac circulation

  • 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

11

GI Tract Circulation

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

  • 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

12

Cutaneous Circulation

  • General
  • Temperature
  • Bradykinin

  • 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

13

The Fick Principle

  • 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