Vascular Control Distribution

MAP and determinants of arterial pressure

• Mean arterial pressure (MAP) is the product of cardiac output and total peripheral resistance: MAP = CO \times TPR
• Cardiac output (CO) is the product of heart rate and stroke volume: CO = HR \times SV
• Determinants of CO include venous return (preload), end-diastolic volume, autonomic influences on heart rate and contractility, and the Frank–Starling mechanism
• Blood viscosity and arteriolar radius are major determinants of Total Peripheral Resistance (TPR)
• Blood flow distribution to organs depends on upstream/downstream vascular resistance and arteriolar radius; Local metabolic activity can override global signals in particular beds
• Blood volume and heart–lung interactions influence venous return and hence end-diastolic volume
• At rest, typical values (from slides):
  • Blood volume ≈ 5 L
  • Cardiac output ≈ 5 L/min
  • Resting heart rate ≈ 60 beats/min
• During moderate exercise, CO can rise to about 12.5 L/min
• Organ blood flow distribution at rest (approximate from slide visuals):
  • Brain: ~13% (~0.65 L/min)
  • Skeletal muscle: ~27% (~1.35 L/min)
  • Liver: ~20% (~1.00 L/min)
  • GI (intestines): ~15% (~0.75 L/min)
  • Kidneys: ~9% (~0.45 L/min)
  • Skin: ~13% (~0.65 L/min)
  • Other: ~3% (~0.15 L/min)
  • Lungs not explicitly listed in the same percentages but are part of the total CO
• Key questions addressed in the lecture:
  • Factors regulating mean arterial pressure
  • Intrinsic vs extrinsic control of blood flow
  • Local factors modifying tissue blood flow
  • Short-term vs long-term regulation of BP and examples

Intrinsic vs extrinsic control of blood flow

• Intrinsic (local/metabolic) control aims to match tissue perfusion to metabolic demand
• Extrinsic (neural and hormonal) control adjusts pressure and distribution system-wide via SNS, PNS, vasopressors
• Local metabolic activity can override the systemic state to maintain tissue viability
• The organ-specific balance: brain and myocardium rely more on intrinsic control; kidney and skin rely more on extrinsic control; skeletal muscle shows balance that changes with activity

Local control of arteriolar tone

• Arterioles are resistance vessels formed by circular smooth muscle; richly innervated by sympathetic nerves
• Vasoconstriction: smooth muscle contraction reduces radius, increases resistance, reduces flow
• Vasodilation: relaxation increases radius, lowers resistance, increases flow
• Basal vascular tone (myogenic tone) varies by organ (e.g., myocardium vs kidney)
• Local metabolic activity drives changes in arteriolar radius:
  • Metabolic factors: increased CO2, H+, K+, adenosine; decreased O2 stimulate vasodilation to raise local flow
  • Temperature effects: cooling reduces diameter; warming promotes dilation
  • Humoral factors: histamine (inflammation) and adenosine mediate vasodilation; bradykinin also increases flow
  • Endothelial mediators: nitric oxide (NO) promotes vasodilation; endothelin promotes vasoconstriction
  • Role of endothelin and NO is regulated by local tissue oxygen requirements to match flow to demand
• Local metabolic activity is summarized as “Local Metabolic Activity” driving arteriolar responses

Short-term nervous control of BP (rapid, nervous control)

• Time course and power:
  • Rapid: seconds to minutes; fastest and most powerful
  • Delayed: minutes to hours; intermediate and can outlast nervous fatigue
  • Long-term: hours to days; involves blood volume regulation; theoretically infinite gain (can return BP to normal)
• Primary rapid regulators: Baroreceptors
• Baroreceptor function:
  • Baroreceptors are stretch receptors located mainly in the carotid sinus and aortic arch
  • They sense arterial wall stretch which correlates with MAP
  • Afferent signals are processed in the medulla to adjust autonomic outflow
• Dynamic vs static baroreflex:
  • Dynamic response: large, rapid depolarization with a sudden BP rise or fall
  • Static response: smaller, sustained depolarization with steady-state changes
• Reflex outcomes:
  • Increased MAP leads to increased baroreceptor firing, which reduces sympathetic outflow to blood vessels and heart and increases parasympathetic activity -> vasodilation, bradycardia, reduced contractility
  • Decreased MAP has opposite effects
• Baroreceptor control across daily activities is precise but has limitations for long-term BP control
• Baroreceptor resetting:
  • Acute changes are buffered by the reflex; long-term changes reset to operate around a higher or lower baseline due to chronic changes in MAP
• Baroreceptor anatomy and physiology notes:
  • Baroreceptors are located near the aortic arch and carotid sinuses; carotid baroreceptors are more sensitive than those in the aorta
  • Chemoreceptors near the aortic and carotid bodies detect changes in O2, CO2, and H+, and influence baroreflex activity
• Baroreceptor reflex diagrammatic points (summary):
  • Step increase in pressure depolarizes baroreceptors → increased afferent activity to vasomotor center → decreased sympathetic outflow and increased parasympathetic outflow → BP returns toward setpoint
  • Step decrease in pressure leads to opposite changes to restore BP
• Baroreceptor relationships to BP: a curve showing phasic (dynamic) and static (tonic) responses; carotid sinus vs aortic arch dynamics
• Long-term baroreflex and denervation data:
  • Baroreceptor-denervated animals show a much wider BP fluctuation range, illustrating loss of buffering capability

Extrinsic vasoconstrictor control (neural and hormonal)

• Peripheral nervous system components:
  • Sympathetic nervous system (vasomotor nerves) originate in the vasomotor center, travel down the spinal cord, synapse in sympathetic ganglia, and innervate most organs
  • Parasympathetic nerves have a limited vascular distribution impact; main actions are on heart via ACh on muscarinic receptors; little direct vascular effect in most systemic beds
  • Sympathetic nerves also reach the heart; parasympathetic input to the heart is relatively modest
• Neurotransmitters and receptor types:
  • Sympathetic postganglionic fibers release norepinephrine (NE), acting on
  • α1-adrenoreceptors: vasoconstriction in most vascular beds
  • β2-adrenoreceptors: vasodilation in heart, lungs, and skeletal muscle with adrenaline predominance
  • Parasympathetic postganglionic fibers release acetylcholine (ACh) acting on muscarinic receptors (limited vascular action)
• Termination of autonomic effects:
  • Parasympathetic: acetylcholinesterase degrades ACh
  • Sympathetic: NE termination via reuptake into nerve terminals, reuptake by extraneuronal uptake, MAO, COMT and other enzymatic pathways
• Extrinsic vasoconstrictor control matrix:
  • Autonomic nervous system (sympathetic and parasympathetic inputs)
  • Central nervous system and peripheral nerves as regulators
  • Target organs and proximal ganglia involved in controlling vascular tone
• Subtype control in specific beds:
  • α-receptor mediated vasoconstriction is dominant in most beds except brain
  • β2-receptor mediated vasodilation is prominent in arterioles of heart, lungs, and skeletal muscle (high adrenaline sensitivity)

The Renin–Angiotensin–Aldosterone System (RAAS)

• Core pathway:
  • Angiotensinogen (from liver) is cleaved by renin (from kidneys) to form angiotensin I
  • Angiotensin-converting enzyme (ACE, primarily in lungs) converts Ang I to angiotensin II (Ang II)
  • Ang II exerts potent vasoconstrictor effects and stimulates aldosterone release from adrenal cortex
• Effects of Ang II and aldosterone:
  • Vasoconstriction increases MAP
  • Aldosterone increases Na+ reabsorption in the distal nephron, expanding extracellular fluid volume
  • Ang II stimulates thirst and promotes antidiuretic hormone (ADH, vasopressin) release
  • Net effect: increased effective circulating volume and arterial pressure
• Hormonal interactions:
  • Vasopressin (AVP/ADH) acts to conserve water, increasing plasma volume
  • Aldosterone acts on renal tubules to retain Na+ and water
• Important clinical note:
  • ACE inhibitors and Ang II receptor blockers (ARBs) blunt this system and lower BP
• Renal–vascular connections:
  • JGA (juxtaglomerular apparatus) senses perfusion pressure and sodium delivery
  • Macula densa cells detect NaCl concentration and modulate renin release
• roles within the system:
  • Increased BP, decreased NaCl delivery, and decreased extracellular volume reduce renin release

Atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH, vasopressin)

• ANP:
  • Released from atrial myocytes in response to atrial stretch (increased blood volume)
  • Causes renal vasodilation of the afferent arteriole and promotes natriuresis (Na+ excretion)
  • Promotes diuresis and reduces blood volume; inhibits renin and aldosterone release
• ADH (vasopressin):
  • Secreted by the posterior pituitary in response to increased plasma osmolality or reduced blood volume
  • Promotes water reabsorption in the collecting ducts, increasing blood volume
  • In high concentrations, contributes to vasoconstriction via V1 receptors
• Interactions:
  • ANP reduces NaCl reabsorption and overall blood volume; decreases ADH release
  • A balance among ANP, ADH, and RAAS determines long-term plasma volume and BP
• Overall signposts:
  • ANP acts to lower BP and volume; RAAS tends to raise BP and volume; ADH can support volume maintenance when needed

Cardiopulmonary (low-pressure) baroreceptors and the Bainbridge reflex

• Cardiopulmonary baroreceptors:
  • Low-pressure receptors located in the atria, ventricles, and great veins
  • Respond to central volume status and venous return; influence renal and vascular tone indirectly
• Bainbridge reflex (atrial stretch reflex):
  • Increased venous return stretches the atria, increasing HR and promoting diuresis to normalize volume
• Net effects on BP and CO:
  • Low-pressure receptors provide indirect feedback to adjust BP via renal and vascular mechanisms in concert with high-pressure baroreceptors

Chemoreceptors and their influence on BP

• Peripheral chemoreceptors (carotid body and aortic arch):
  • Detect decreases in PaO2, increases in PaCO2, and H+ (acidity)
  • Activate CNS vasoconstrictor regions and boosts sympathetic outflow, with a secondary role in BP control (mainly to regulate ventilation; minor BP effects at normal pressures)
• Central chemoreceptors (medulla):
  • Activated by high PaCO2 and H+ in CSF
  • Cause marked vasoconstriction and increased peripheral resistance, producing a strong BP response
• Forced apnea and chemoreceptor synergy:
  • Under hypoxic conditions, peripheral and central chemoreceptors act together to enhance vasoconstriction and stimulate the heart

Autoregulation and local blood flow control

• Autoregulation goal:
  • Ensure local perfusion matches tissue demand independently of systemic BP changes
• Mechanisms and factors:
  • Temperature changes: cooling reduces diameter; warming increases diameter
  • Myogenic mechanism: vessels constrict when stretched; dilate when distended
  • Metabolic factors: ↑ CO2, H+, K+, adenosine; ↓ O2 promote vasodilation locally
  • Humoral factors: histamine (inflammation) promotes dilation; adenosine enhances metabolic dilation in heart; bradykinin contributes to dilation in some tissues
  • Endothelial factors: NO promotes vasodilation; endothelin promotes vasoconstriction
• Tissue-specific roles:
  • Brain and myocardium rely more on intrinsic control (tightly matched to O2 demand)
  • Kidney and skin rely more on extrinsic control for BP homeostasis
• Autoregulation and MAP/CO relationship:
  • MAP ≈ TPR × CO; local autoregulation can adjust TPR independent of central commands
  • A modest rise in CO (e.g., ~5%) can produce a large rise in MAP if autoregulatory responses are overwhelmed; conversely, MAP can be stabilized by local vasoconstrictor/vasodilator adjustments

Reactive and active hyperemia (special cases of local flow control)

• Reactive hyperemia:
  • Restoration of blood flow after a transient block; flow increases to well above normal levels for a period
  • Time course of increased flow is related to the duration of the occlusion; metabolically mediated
• Active hyperemia:
  • Increased blood flow to metabolically active tissue (e.g., exercising muscle) to meet heightened demand
  • Similar mechanism to reactive hyperemia, driven by local metabolic byproducts and endothelial signaling

Long-term regulation of Blood Pressure and Blood Volume (renal control)

• Long-term BP regulation is primarily via renal handling of volume rather than rapid baroreceptor adjustments
• Key relation:
  • MAP = CO × TPR (as above), but CO is modulated over longer times by heart rate, stroke volume, and venous return; changes in blood volume alter venous return and hence end-diastolic volume
• Renal mechanisms: pressure diuresis and pressure natriuresis
  • When arterial pressure rises, the kidneys excrete more water and salt to reduce blood volume and BP; when BP falls, kidneys conserve Na+ and water
• Neural and hormonal pathways influencing long-term BP:
  • Atrial stretch receptors contribute to renal arteriolar dilation, increasing GFR and promoting diuresis
  • Reduced ADH release and increased ANP production promote natriuresis and diuresis
  • The RAAS acts to restore circulating volume via sodium and water retention when blood volume falls
• The integrated renal control network (as per slides):
  • Atrial stretch receptors, GFR changes, ANP, renin release, ANG II, aldosterone, ADH, central nervous system inputs, and liver/kidney interactions
• Experimental insight:
  • Neural block plus blood infusion can raise BP and CO, but BP normalizes with fluid loss via renal excretion, illustrating kidney-dominant long-term BP control
• Summary of long-term regulators:
  • Increase in BP → pressure diuresis and natriuresis; decrease in BP → renal conservation of Na+ and water
• Practical implications:
  • The renal body-fluid mechanism is the dominant long-term regulator of arterial pressure, while neural baroreceptors are critical for rapid adjustments

Integration and comparative view of circulatory control mechanisms

• Integrated view:
  • Metabolic (intrinsic) control and neural (extrinsic) control operate together to regulate tissue perfusion and BP
  • Brain and myocardium are intrinsically driven and intolerant of low flow
  • Kidney and skin are more dependent on extrinsic control for BP homeostasis
  • Skeletal muscle regulation is situation-dependent: neural control dominates at rest (vasoconstriction) and at exercise onset; metabolic regulation becomes more prominent as activity continues
• Special notes on control hierarchy:
  • Local metabolic demands can override systemic signals to ensure tissue viability
  • RAAS and ADH/ANP provide longer-term volume and pressure adjustments, adjusting SV and venous return over time
• Autoregulation and its limits:
  • Local vasodilation and vasoconstriction adjust flow without requiring neural input, but extreme changes can still be managed by central reflexes and renal adjustments
• Summary of principal control pathways (concise map):
  • End point: Mean arterial pressure and tissue perfusion maintained by the interplay of:
  • Local metabolic activity, endothelial signaling (NO, endothelin), and autoregulation
  • Extrinsic sympathetic and parasympathetic innervation with β2 and α receptors dictating vasodilation/vasoconstriction
  • Hormonal systems: RAAS, AVP/ADH, and ANP regulate blood volume and vascular tone
  • Renal mechanisms ensure long-term stability by adjusting blood volume via diuresis and natriuresis

Quick reference formulas and numerical anchors

• MAP relation: MAP = CO \times TPR
• CO relation: CO = HR \times SV
• Autoregulation summary: local flow adjusts to tissue perfusion without requiring large changes in MAP; overall MAP can be shifted by changes in CO and TPR but autoregulation moderates that effect
• Blood volume and venous return link to end-diastolic volume and stroke volume via the Frank–Starling mechanism
• Renin–angiotensin–aldosterone system (RAAS) pathway (simplified):
  • Renin\;\rightarrow\; Angiotensin I\;\rightarrow\; Angiotensin II (via ACE in lungs)
  • Ang II promotes vasoconstriction and aldosterone release; aldosterone increases Na+ reabsorption and water retention
• ANP/ADH interplay:
  • ANP promotes natriuresis and diuresis, lowers blood volume; ADH promotes water conservation
• Key regulatory receptors distribution (simplified):
  • α-adrenoceptors: vasoconstriction in most beds
  • β2-adrenoceptors: vasodilation in heart, lungs, skeletal muscle beds (predominantly with adrenaline)

Notes on key takeaways for exam preparation

• Short-term BP control relies mainly on baroreceptor reflexes with rapid adjustments in HR, SV, and vascular tone; long-term BP control is renal-body-fluid regulation via diuresis, natriuresis, and RAAS modulation
• Local autoregulatory mechanisms ensure tissue perfusion aligns with metabolic demand, with NO promoting dilation and endothelin promoting constriction
• Systemic hormonal control (RAAS, AVP, ANP) modulates blood volume and vascular tone to maintain BP over hours to days
• The distribution of blood flow at rest emphasizes that brain and muscles receive different shares of CO; during exercise, distribution shifts to active muscles and skin for heat dissipation while maintaining perfusion to essential organs
• Baroreceptor resetting is a critical concept: rapid control is effective but not a long-term solution for chronic BP changes