Sympathetic and Parasympathetic Nervous System Responses and Receptor Functions
The sympathetic and parasympathetic nervous systems have opposing effects on body systems, with alpha receptors primarily mediating vasoconstriction, beta receptors controlling cardiac function and vasodilation, and cholinergic antagonists blocking parasympathetic effects by inhibiting acetylcholine action.
Sympathetic Nervous System Effects
The sympathetic nervous system produces the "fight or flight" response through the release of catecholamines (norepinephrine and epinephrine) that act on adrenergic receptors 1. Key effects include:
Cardiovascular effects:
- Increased heart rate and contractility
- Peripheral vasoconstriction (primarily in skin and kidneys)
- Increased blood pressure
- Coronary vasodilation
Respiratory effects:
- Bronchodilation
- Increased respiratory rate
Metabolic effects:
- Increased blood glucose via glycogenolysis
- Increased lipolysis
- Increased metabolic rate
Other effects:
- Pupil dilation
- Decreased gastrointestinal motility
- Increased sweating
Parasympathetic Nervous System Effects
The parasympathetic nervous system produces "rest and digest" responses through acetylcholine acting on muscarinic receptors 2, 3:
Cardiovascular effects:
- Decreased heart rate (bradycardia)
- Decreased cardiac contractility
- Minimal effect on vascular tone
Respiratory effects:
- Bronchoconstriction
- Increased bronchial secretions
Digestive effects:
- Increased gastrointestinal motility
- Increased digestive secretions
Other effects:
- Pupil constriction
- Increased salivation
- Increased urinary bladder contraction
Adrenergic Receptor Functions
Alpha-1 Receptors
- Location: Primarily postsynaptic on vascular smooth muscle, urinary tract, and heart 4, 1
- Signaling: Coupled to Gq proteins, activate phospholipase C
- Effects:
- Vasoconstriction (especially in skin and kidneys)
- Urinary sphincter contraction
- Can increase heart rate directly 5
- Pupil dilation
Alpha-2 Receptors
- Location: Presynaptic nerve terminals, central nervous system, platelets 4, 1
- Signaling: Coupled to inhibitory Gi proteins, decrease cAMP production
- Effects:
- Inhibit norepinephrine release (presynaptic)
- Decrease central sympathetic outflow
- Decrease blood pressure when activated in CNS
- Platelet aggregation
Beta-1 Receptors
- Location: Predominantly in heart, also in brain and adipose tissue 4, 6, 1
- Signaling: Coupled to stimulatory Gs proteins, activate adenylyl cyclase-cAMP pathway
- Effects:
- Positive chronotropic effect (increased heart rate)
- Positive inotropic effect (increased contractility)
- Increased renin release from kidneys
- Increased lipolysis in adipose tissue
Beta-2 Receptors
- Location: Bronchial smooth muscle, blood vessels, uterus, GI tract 4, 6, 1
- Signaling: Coupled to stimulatory Gs proteins, activate adenylyl cyclase-cAMP pathway
- Effects:
- Bronchodilation
- Vasodilation (especially in skeletal muscle)
- Uterine relaxation
- Decreased GI motility
- Glycogenolysis in liver
- Decreased platelet aggregation
Beta-3 Receptors
- Location: Adipose tissue 1
- Signaling: Can couple to both stimulatory and inhibitory G proteins
- Effects:
- Increased lipolysis
- Increased thermogenesis
- Improved insulin sensitivity
Cholinergic Antagonists (Anticholinergics)
Cholinergic antagonists block the effects of acetylcholine at muscarinic receptors, inhibiting parasympathetic nervous system effects 7. Key drugs include:
Quaternary Ammonium Compounds (Limited CNS penetration)
Glycopyrrolate:
- Inhibits acetylcholine action on structures innervated by postganglionic cholinergic nerves
- Reduces secretions (gastric, bronchial, salivary)
- Antagonizes muscarinic symptoms (bronchorrhea, bronchospasm, bradycardia)
- Limited CNS effects due to poor blood-brain barrier penetration 7
- Used for preoperative reduction of secretions, reversal of neuromuscular blockade, and treatment of peptic ulcers
Ipratropium:
- Bronchodilator for COPD and asthma
- Reduces bronchial secretions
- Minimal systemic effects
Tiotropium:
- Long-acting bronchodilator for COPD
- Once-daily dosing
Tertiary Amines (Greater CNS penetration)
Atropine:
- Blocks muscarinic receptors in heart, bronchi, GI tract, eye, and bladder
- Increases heart rate by blocking vagal influence
- Dilates pupils and paralyzes accommodation
- Used for bradycardia, organophosphate poisoning, and as a preoperative medication
Scopolamine:
- Similar to atropine but with more pronounced CNS effects
- Used for motion sickness and as an antiemetic
- Causes amnesia and sedation
Benztropine:
- Used for Parkinson's disease and drug-induced extrapyramidal symptoms
- Blocks central muscarinic receptors
Clinical Implications and Interactions
- The sympathetic and parasympathetic systems interact at multiple levels, not just as opposing forces 3
- Heart rate variability reflects the balance between sympathetic and parasympathetic inputs, with high-frequency components primarily reflecting vagal activity 8
- Long-term sympathetic activation in heart failure leads to deleterious effects including vasoconstriction, cardiac hypertrophy, arrhythmias, and programmed cell death 2
- Beta-blockers in heart failure counteract these harmful effects of sympathetic activation, improving survival 2
- Alpha-1 receptor activation can both increase heart rate directly and decrease it indirectly through parasympathetic activation 5
Understanding these complex interactions is crucial for appropriate pharmacological management of cardiovascular, respiratory, and other autonomic disorders.