Central, Neural & Humoral Control of Blood Pressure Montemayor Monday Lecture 2

CENTRAL NEURAL & HUMORAL CONTROL OF BLOOD PRESSURE

Author: Jennifer Montemayor, Ph.D.
Institution: Alberta, Canada
Email: jmontemayor@rvu.edu

CLINICAL CONTEXT

  • A case study of a 22-year-old male college student who sustained multiple stab wounds.

  • Emergency Situation: A witness calls 911 after seeing the patient in distress.

  • Vital Signs Recorded:

    • Heart Rate (HR): 128 bpm

    • Blood Pressure (BP): 80/55 mmHg

    • Respiratory Rate (RR): 37 breaths per minute

  • Patient Condition:

    • Patient conscious but confused, exhibiting high anxiety and severe pain.

    • Reports sensation of heart pounding in chest.

    • Physical examination reveals:

    • Absent pedal pulses

    • Weak radial pulses

    • Palpable carotid pulses

    • Cool and clammy skin with poor turgor.

  • Immediate Intervention:

    • Administered I.V. lactated Ringer’s solution at a rate of 150 ml/hr.

    • Estimated blood loss of approximately 20-25% of total blood volume.

  • Diagnosis: Hypovolemic hemorrhagic shock.

    • Definition: Rapid fluid loss (whole blood, plasma, or other extracellular fluid [ECF]) leading to inadequate tissue perfusion and potential hypoxic damage, possibly resulting in organ failure. Hemorrhagic shock defined as a loss of ≥ 20% of total blood volume.

UNDERSTANDING BLOOD PRESSURE REGULATION

  • Foundational Concepts:

    • Essential knowledge needed to understand this case.

  • Key Questions Addressed in the Lecture:

    1. What is the most critical cardiovascular (CV) variable monitored and regulated by the body?

      1. The most critical cardiovascular (CV) variable monitored and regulated by the body is blood pressure, as it is vital for ensuring adequate blood flow to organs and tissues.

    2. What sensory receptors detect changes during hemorrhage?

      1. Baroreceptors and chemoreceptors play a key role in detecting changes during hemorrhage, as they sense variations in blood pressure and chemical composition, respectively, prompting appropriate neurohumoral responses.

    3. What are the neural responses to decreased Mean Arterial Pressure (MAP)?

      1. When there is a decrease in Mean Arterial Pressure (MAP), neural responses include activation of the sympathetic nervous system, which leads to increased heart rate and myocardial contractility, as well as vasoconstriction of peripheral blood vessels, helping to restore blood pressure levels.

    4. What are the humoral responses to decreased MAP?

      1. Humoral responses to decreased MAP involve the release of hormones such as renin from the kidneys, which catalyzes the formation of angiotensin II, a potent vasoconstrictor, and stimulates aldosterone secretion to promote sodium and water retention, thereby increasing blood volume.

OBJECTIVES

  1. Explain the importance of blood pressure maintenance for the cardiovascular system's function.

  2. Classify receptors involved in neural regulation of blood pressure regarding:

    • Location

    • Variables to which each responds

    • Effectors of reflexes initiated by each

    • Impact on MAP

  3. Describe the integrated physiological response to central chemoreceptor activation.

  4. Compare and contrast sympathetic and parasympathetic effects on MAP, including:

    • Input to heart and vasculature

    • Primary effectors

    • Neurotransmitters and receptors

    • Effects on major ion currents linked with each autonomic nervous system division.

  5. List major vasoactive endocrine/paracrine compounds and their effects on vasomotor tone.

    1. Norepinephrine: Potent vasoconstrictor that increases blood pressure by stimulating alpha-adrenergic receptors.

    2. Epinephrine: Modifies vascular tone by acting on both alpha and beta receptors, leading to vasoconstriction in some vascular beds and vasodilation in others.

    3. Angiotensin II: Strong vasoconstrictor that raises blood pressure and promotes sodium retention through its action on AT1 receptors.

    4. Atrial Natriuretic Peptide (ANP): Reduces blood pressure by promoting vasodilation and natriuresis, counteracting the effects of other vasoactive substances.

    5. ADH: Antidiuretic hormone (ADH), also known as vasopressin, increases blood pressure by promoting water reabsorption in the kidneys, which reduces urine output and increases blood volume.

  6. Compare and contrast α1 and β2 receptors regarding affinity for epinephrine and norepinephrine and their effects on smooth muscle tone.

    1. α1 Receptors: Primarily respond to norepinephrine and have a higher affinity for it, leading to smooth muscle contraction and vasoconstriction, which raises blood pressure.

    2. β2 Receptors: Have a higher affinity for epinephrine, resulting in smooth muscle relaxation and vasodilation, which lowers blood pressure.

  7. Assess the role of the following in humoral regulation of MAP:

    • Renin-Angiotensin-Aldosterone System

    • Atrial Natriuretic Hormone

    • Antidiuretic Hormone / Vasopressin

    • Discuss receptor location, stimuli, variable(s) altered in response, and overall effects on blood pressure for each.

NEURAL ACTIVATION OF HEART AND BLOOD VESSELS

  • Key Components:

    • Autonomic innervation of the heart and blood vessels.

    • Release and influence of circulating catecholamines.

    • Function of adrenergic and cholinergic receptors in blood vessel dynamics.

    • Role of arterial baroreceptors.

    • Mechanism of Renin-Angiotensin-Aldosterone system and vasopressin/antidiuretic hormone.

    • Function of Atrial Natriuretic Peptide (Hormone).

OVERVIEW OF BLOOD PRESSURE REGULATION

I. INTRODUCTION

  • Review of factors determining and regulating MAP.

II. CENTRAL NEURAL REGULATION OF MAP

A. Short-term Regulation of MAP

  • Key Concepts:

    • Effects of the Sympathetic Nervous System on MAP (affecting Heart Rate [HR], Stroke Volume [SV], Total Peripheral Resistance [TPR]).

    • Effects of the Parasympathetic Nervous System on MAP.

    • Neural Reflexes:

    1. Integration Center

    2. Receptors

      • High-Pressure Baroreceptors

      • Low-Pressure Baroreceptors

      • Chemoreceptors

B. Humoral Regulation of MAP

  • Intermediate- and Long-term Regulation of MAP:

    • Regulation of vascular resistance (vasoactive substances.)

    • Regulation of Na+ and H2O (blood volume):

    1. Renin-Angiotensin-Aldosterone System

    2. Antidiuretic Hormone (ADH)/Arginine Vasopressin (AVP)

    3. Atrial Natriuretic Peptide (Hormone)

MEAN ARTERIAL BLOOD PRESSURE (MAP)

  1. Key Variable Monitored by CV System:

    • Definition:

    • MAP ensures adequate driving force for blood flow to supply organs.

    • Organ blood flow regulated by arteriolar resistance control.

    • Functionality:

    • Maintains that alterations in blood flow to one tissue do not significantly affect others (supply according to demand).

    • Mathematical Representation:
      MAP=COimesTPRMAP = CO imes TPR

    • Where:

      • CO = Cardiac Output

      • TPR = Total Peripheral Resistance

TIMING OF MAP REGULATION

  • Short-term: Seconds to minutes (Neural Regulation)

  • Key Effectors:

    • Cardiac (SA node, myocardium)

    • Vascular smooth muscle cells (VSMCs)

    • Adrenal medulla

  • Long-term: Hours to days (Endocrine/Paracrine Regulation)

  • Key Effectors:

    • Vascular smooth muscle cells (VSMCs)

    • Kidneys (regulating blood volume)

II. CENTRAL NEURAL CONTROL OF MAP

A. Sympathetic Effects on MAP

  1. Summary of Sympathetic Influence:

    • Increases in MAP due to:

      • Increased Cardiac Output (CO)

      • Increased Heart Rate (HR)

      • Increased Conduction Velocity

      • Increased Contractility (SV)

      • Increased Relaxation Rate

      • Increased Total Peripheral Resistance (TPR)

      • Increased Vasoconstriction

    • Mathematical Representation:
      MAP=HRimesSVimesTPRMAP = HR imes SV imes TPR

B. Sympathetic Influence of MAP: Adrenal Medulla

  • Mechanism:

    • Sympathetic input to adrenal medulla promotes epinephrine release into the bloodstream.

    • Effects:

    • Epinephrine impacts the heart and vasculature, contributing to humoral blood pressure regulation.

NEURAL REGULATION REVIEW: SYMPATHETIC NERVOUS SYSTEM

A. Heart Rate Overview

  1. Norepinephrine Effects (β1 Agonists):

    • Increases If (funny current) leading to:

    • Increased slow depolarization rate (increased steepness of phase 4).

    • Increased ICa in myocardial cells.

    • Threshold voltage becomes more negative (reached sooner).

    • Decreased IK (potassium current) affecting phase 4 depolarization.

    • Resulting in a shorter time for depolarization to threshold, thus increasing heart rate.

B. Sympathetic Influence on Contractility

  • Mechanism:

    1. Increased Ca2+ influx via L-type DHDP channels.

    2. Increased sensitivity of RYR (ryanodine receptors) to intracellular Ca2+ ([Ca2+]i).

    3. Enhanced SERCA activity (removal of phospholamban inhibition) thereby increasing Ca2+ stores.

  • Outcome: Results in increased force of contraction, elevating Cardiac Output (CO).

C. Sympathetic Control of Total Peripheral Resistance (TPR)

  • Mechanism:

    • Postganglionic sympathetic fibers innervate muscular arteries, arterioles, and veins producing vasoconstriction.

    • Receptor Dynamics:

    • Vasoconstrictor sympathetic fibers are most concentrated in the kidney and skin, least in the heart and brain.

    • Norepinephrine acts on α₁-adrenergic receptors on vascular smooth muscle cells, causing generalized vasoconstriction (pressor effect).

    • Skeletal and cardiac muscle can experience vasodilation due to sympathetic response activating β2 receptors.

II.B. PARASYMPATHETIC NERVOUS SYSTEM AND MAP

  1. Summary of Parasympathetic Influence:

    • Decreases in MAP due to:

      • Decreased CO

      • Decreased HR

      • Decreased Conduction Velocity

      • Some reduction in contractility

      • Minimal Influence on TPR

    • Mathematical Representation:
      MAP=HRimesSVimesTPRMAP = HR imes SV imes TPR

B. Parasympathetic Influence on Heart Rate

  • Mechanism:

    • Slows down the depolarization rate (decreased steepness of phase 4).

    • Makes the threshold more positive (takes longer to reach).

    • Results in longer time for depolarization to threshold, decreasing heart rate.

C. Minimal Influence on Total Peripheral Resistance (TPR)

  • Reasons:

    • Parasympathetic nervous system has fewer vasodilator fibers than sympathetic vasoconstrictor fibers.

    • Active mainly in specific vascular regions such as coronary vessels and salivary's arteries.

    • Indirect vasodilation via acetylcholine release impacting vascular smooth muscles.

II.C. NEURAL REFLEXES IN MAP REGULATION

1. Integration Center

  • Medullary Cardiovascular Center:

    • Critical for MAP homeostasis regulation.

    • Mediates both sympathetic and parasympathetic effects.

    • Receives inputs from:

    • Baroreceptors (high and low pressure)

    • Chemoreceptors

    • Hypothalamus

    • Cerebral cortex

    • Skin

    • Local CO2 and O2 concentrations

2. Regulation of MAP: Receptors and Reflex pathways

  • Key Receptors:

    • Baroreceptors (mechanoreceptors detecting stretch):

      • High-pressure: carotid sinus & aortic arch

      • Low-pressure: vena cava & atrium.

    • Chemoreceptors: detect changes in blood PO2, Pco2, [H+].

  • Integration Center:

    • CNS, with primary site being the medulla oblongata.

  • Effectors:

    • Cardiac myocytes, arterial & venous VSMCs, adrenaline secretion via adrenal medulla, and kidneys.

III. HUMORAL REGULATION OF MAP

A. Regulation of Vascular Resistance

  • Overview:

    • Vasoactive substances interact with vascular smooth muscle to alter resistance and thus MAP.

    • Vasoactive factors:

    • Can be amines, peptides, proteins, derivatives of arachidonic acid, or gaseous substances like Nitric Oxide (NO).

B. Major Endocrine Factors Regulating MAP

  1. Epinephrine:

    • Action: Vasoconstriction via α₁ receptors, vasodilation via β₂ receptors, primarily from adrenal medulla.

  2. Angiotensin II (ANG II):

    • Produced by ACE converting ANG I, influencing vasoconstriction, primarily during blood loss or exercise.

  3. Antidiuretic Hormone (ADH): Also known as Arginine Vasopressin (AVP), promotes water retention and vasoconstriction.

  4. Histamine:

    • Released in response to tissue trauma, inducing vasodilation.

  5. Atrial Natriuretic Peptide (ANP/ANH):

    • Secreted from cardiac atrial cells in response to increased stretch, acting as both a vasodilator and natriuretic agent (promoting sodium excretion).

III. SUMMARY OF ENDOCRINE REGULATION

A. Feedback Controls Affecting Effective Circulating Volume

  • The Mechanism: When effective circulating volume is low, triggers multiple effector pathways acting on the kidney to affect hemodynamics or influencing sodium transport in renal tubule cells.

  • Assistance from Autonomic Nervous System (ANS): Plays an essential role in integrated responses, affecting blood volume regulation.

B. Key Hormones Overview for MAP Regulation

  1. Renin-Angiotensin-Aldosterone System (RAAS): Increases MAP.

  2. ADH/Vasopressin: Increases MAP.

  3. Atrial Natriuretic Hormone: Decreases MAP.