Cardiovascular System Regulation I

Regulation of the Cardiovascular System

• Regulation occurs in the heart (cardiac output) and circulation.
• Cardiac output regulation involves both heart rate and stroke volume.
• Circulation regulation involves local and general controls.
  • General controls affect mean arterial pressure (MAP) and extracellular fluid (ECF) volume.
  • General includes short-term (nervous), intermediate (humoral), and long-term mechanisms (pressure diuresis and natriuresis).

Regulation of Arteriolar Smooth Muscle

• Myogenic contraction is an intrinsic, basal activity of arteriolar smooth muscle, independent of neural, hormonal, and paracrine input.
• Local control mechanisms are independent of nerves and hormones, representing self-regulation.
  • Active hyperemia, flow autoregulation, reactive hyperemia, and response to injury are examples of local control.
• Extrinsic control comes from:
  • Sympathetic nerves
  • Other nerves
  • Hormones
  • Vasoactive substances
• Endothelial cells help with extrinsic control.

Regulation of Systemic Arterial Pressure

• Mean Arterial Pressure (MAP) is the product of Cardiac Output (CO) and Total Peripheral Resistance (TPR): MAP = CO x TPR
• MAP is regulated by changes in cardiac output and total peripheral resistance.

Cardiac Output and its Determinants

• Cardiac output is determined by stroke volume and heart rate.
• Stroke volume depends on inotropy and ventricular preload.
• Ventricular preload is altered by changes in venous compliance and blood volume.
  • Decreased venous compliance (veins constricting) increases ventricular preload and central venous pressure.
• Total blood volume is regulated by renal function, in particular renal handling of sodium and water.
• Heart rate, inotropy, venous compliance, and renal function are all strongly influenced by neurohumoral mechanisms.

Total Peripheral Resistance (TPR)

• TPR relies on the anatomy of the vascular network (series vs. parallel resistance elements).
• Changes in vessel lumen diameter is the most important mechanism of changing TPR.
  • According to the Poiseuille relationship, resistance is inversely related to the fourth power of the vessel radius.
  • F = ΔPπr4/8ηL (F = flow, ΔP = pressure difference, r = radius, η = viscosity, L = length).
  • F = ΔP/R
  • R = 8ηL/πr4
• Vascular factors, such as nitric oxide or endothelin, can influence vessel diameter.
• Myogenic mechanisms, intrinsic to the vascular smooth muscle, can also alter vessel diameter.
• Tissue factors (e.g., potassium ion, hydrogen ion, histamine) are chemicals released by parenchymal cells surrounding blood vessels.
  • Tissue factors can significantly alter vessel diameter which affects organ blood flow and systemic arterial pressure.

Nervous Mechanisms of MAP Regulation

• Arterial baroreceptors
• Peripheral chemoreceptors
• Volume receptors (low-pressure baroreceptors)
• Cerebral ischemic response

CNS Areas Linked to Cardiovascular Regulation

• Insular and limbic cortex, amygdala nuclear complex (telencephalon).
• Nucleus hypothalamicus anterior, nucleus hypothalamicus lateralis, nucleus paraventricularis (diencephalon).
• Nucleus parabrachialis lateralis, periaqueductal grey (mesencephalon).
• Area postrema, nucleus tractus solitarii, Ncl. Ambiguus/Ncl. Dorsalis N. Vagi, medulla ventrolateralis caudalis, medulla ventrolateralis rostralis (pons a medulla oblongata).
• Nuclei Intermediolateralis (medulla spinalis)

Autonomic Nervous System

• Sympathetic and parasympathetic divisions.
• Includes anatomy, functions, and neurotransmitters.

Sympathetic Nervous System (Thoracolumbar Division)

• Preganglionic neurons originate from spinal segments T1-L2 (lateral horns) and release acetylcholine, which binds to cholinergic receptors (N) on postganglionic neurons.
• Postganglionic neurons are located in the sympathetic chain of ganglia (paravertebral) + prevertebral ganglia, release mostly noradrenaline binding on adrenergic receptors (α1, α2, β1, β2) in target tissues.
• The heart mainly has β1 receptors that cause positive chrono-, ino-, and dromotropic effects.
• Vessels have α1 (vasoconstriction) and β2 (vasodilatation) receptors.

Parasympathetic Nervous System (Craniosacral Division)

• Preganglionic neurons originate from cerebral nuclei of cranial nerves III, VII, IX, and X (75%) and release acetylcholine binding on cholinergic receptors (N) on postganglionic neurons.
• Postganglionic neurons are usually in the wall of the innervated organ, release acetylcholine binding on cholinergic receptors (muscarinic) in target tissues.
• The heart is innervated by the vagus nerve (atria only), causing negative chrono-, ino-, and dromotropic effects.
• Vessels have little to no parasympathetic innervation (0, mostly).

Cardiovascular Center / Vasomotor Center

• Located in the reticular substance of the medulla and lower pons

• Vasoconstrictor area (RVLM - rostral ventrolateral medulla) excite preganglionic vasoconstrictor neurons + cardioexcitatory area.

• Vasodilator area (CVLM - caudal ventrolateral medulla) inhibits the vasoconstrictor area.

• Sensory area (NTS) receives impulses through vagus and glossopharyngeal nerves and modulates the activity of the vasoconstrictor and vasodilator areas.

• Cardioinhibitory area = Dorsal motor nucleus of the vagus nerves + nucleus ambiguous.

Baroreceptors

• Located in the walls of arteries, mostly in the internal carotid artery (carotid sinus) and aortic arch
• Baroreceptors are stimulated when stretched with a firing range between 60 to 180 mmHg
• Impulses are transmitted to the sensory area via cranial nerves IX and X.

Baroreceptors Effects

• Inhibition of the vasoconstrictor area.
• Stimulation of the vasodilator area.
• Stimulation of the vagal parasympathetic center.
• Vasodilation and decreased heart rate.

Baroreceptor Characteristic

• Most sensitive around 90 - 110 mmHg.

Baroreceptor Reflex

• Increase in MAP leads to baroreceptor stimulation.
• Systemic venodilation.
• Decreased venous return.
• Decreased CO.
• Arteriolar dilation.
• Decrease in TPR and MAP.
• Increased vasodilator and cardioinhibitory center activity.
• Decreased vasoconstrictor area activity.

Chemoreceptors

• Located in the medulla, glossopharyngeal nerve, vagus nerve, carotid body, and aortic bodies.
• Decreased pO2 (below 60 mmHg) or decreased MAP (below 80 mmHg) and stimulation of peripheral chemoreceptors causes:
  • Vasoconstrictor area stimulation.
  • Increased CO and SVR.
  • Increased MAP.
  • Increased stimulation of ventilation.
  • Increased alveolar ventilation.

Volume Receptors - Atria

• Atrial receptors firing lead to:
  • SNS Activation
• B Receptors firing lead to:
  • Water excretion
  • Decreased MAP

Volume Receptors (B)

• Increased ECF volume leads to increased volume receptors firing.
• Decreased activity of vasoconstrictor area.
• Arteriolar vasodilation.
• Increased capillary BP, ultrafiltration, and decreased intravascular volume.
• Decreased SVR and MAP.
• Activation of hypothalamus.
• Decreased ADH Secretion.
• Afferent arteriole dilation.
• Increased GFR and urine output
• Decreased ECF Volume

Volume Receptors (A) - Bainbridge Reflex

• Increased Atrial pressure and Atrial Stretch
• Increased firing of vagal afferents
• Decrease parasympathetic efferent firing
• Increase sympathetic efferent firing
• Cardiac + Vasomotor Center

Cerebral Ischemic Response

• Decreased MAP below 50 mmHg, Intracranial hypertension, or fall in MAP.
• Ischemia of neurons of the cardiovascular center + CO2 accumulation.
• Increased activity of vasoconstrictor area
• Increased SNS activity
• Extreme increase in MAP (250 mmHg).