PHA 334 - ANS (Lecture #3) AFTER MIDTERM!

Baroreceptor reflex

Regulates blood pressure via autonomic nervous system (SNS/PNS)

Baseline vascular tone

Blood vessels are partially constricted at rest

Low BP response

↑ SNS → ↑ HR, ↑ contractility, vasoconstriction → ↑ BP

High BP response

↓ SNS + ↑ PNS → ↓ HR, vasodilation → ↓ BP

Baroreceptors

Mechanical stretch receptors located in tunica externa of blood vessels

Baroreceptors location

Carotid sinus (CN IX) and aortic arch (CN X)

Baroreceptor pathway

Signals → solitary nucleus (medulla) → autonomic output

Low BP baroreceptor activity

Inhibited → activates cardioacceleratory center, inhibits cardioinhibitory center, stimulates vasomotor center

High BP baroreceptor activity

Stimulated → activates cardioinhibitory center, inhibits cardioacceleratory center and vasomotor center

CO definition

Cardiac output

R definition

Peripheral resistance

BP equation

BP = CO × R

β1 receptor (heart)

↑ HR and ↑ contractility

M2 receptor (heart)

↓ HR

α1B receptor (vessels)

Vasoconstriction

β2 receptor (vessels)

Vasodilation

Vasovagal syncope

Excess vagal activity → ↓ HR/CO → ↓ brain perfusion → fainting

Hypertension main cause

↑ Peripheral resistance (~95%)

CAD (Acute Coronary Syndrome)

Atherosclerosis → plaque → ↓ coronary blood flow

◦Beta-blockers reduce oxygen demand, ischemia, arrhythmia, reinfarction; prevent cardiac remodeling*

the most common type of cardiovascular disease

______ is caused by plaque buildup in the walls of the coronary arteries that supply blood to the heart, narrowing them; this process is called atherosclerosis

Plaque is made up of cholesterol deposits along with aggregated platelets and various immune cells

Beta blockers

β-adrenergic antagonists → ↓ HR, ↓ contractility, ↓ oxygen demand

Beta blocker uses

Hypertension, CAD, arrhythmias, heart failure

Cardioselective β1 blockers (AMEEBA)

Atenolol, Metoprolol, Esmolol, Bisoprolol, Betaxolol, Acebutolol (β1 antagonists)

Selectivity concept

High doses lose β1 selectivity → affect β2 receptors

Atenolol

β1 antagonist → treats hypertension

Metoprolol

β1 antagonist → treats hypertension

Esmolol

β1 antagonist → acute cardiac control

Bisoprolol

β1 antagonist → treats hypertension/heart failure

Betaxolol

β1 antagonist → treats hypertension

Acebutolol

β1 antagonist (partial agonist) → treats hypertension

Labetalol

non selective α1 and β1 antagonist + partial β2 agonist → treats hypertension in pregnancy (pre-eclampsia)

Beta blockers in hypoglycemia

Block β receptors → ↓ HR/tremor but sweating persists via M3

Juxtaglomerular cells

Modified smooth muscle cells that release renin when BP ↓ via β1 stimulation

Macula densa

Chemoreceptors that sense NaCl in filtrate

Extraglomerular mesangial cells

Transmit signals between macula densa and JG cells

RAAS purpose

Increase BP via vasoconstriction and ↑ blood volume

RAAS pathway

Renin → Ang I → ACE → Ang II

Angiotensin II receptor

Acts on AT1 receptors → vasoconstriction and ↑ BP

Angiotensin II effects

AT1 → vasoconstriction, ↑ aldosterone, ↑ ADH, ↑ thirst

Aldosterone effect

↑ Na+ and water reabsorption → ↑ BP

ADH effect

↑ Water reabsorption → ↑ BP

Lisinopril

ACE inhibitor → ↓ Ang II → treats hypertension

Azilsartan

AT1 receptor antagonist → blocks Ang II → treats hypertension

PNS (“rest and digest”)

M2/M3 activation → ↓ HR, ↑ digestion, ↑ secretion

PNS blood vessels

M3 activation → minimal vasodilation

SNS (“fight or flight”)

α/β activation → ↑ HR, ↑ BP, ↑ glucose

Adrenal medulla

Releases epinephrine (80%) and norepinephrine (20%)

Preganglionic NT (ANS)

Acetylcholine (ACh)

PNS receptors

M2 (heart), M3 (smooth muscle/glands)

M3 receptor effects

↑ secretions, ↑ GI motility, bronchoconstriction, bladder contraction

SNS receptors

α1, α2, β1, β2

α1 receptor effects

Vasoconstriction, piloerection, emotional sweating

β2 receptor effects

Smooth muscle relaxation, bronchodilation, skeletal muscle tremors

β1 receptor effects

↑ HR/contractility and ↑ renin release (kidney)

α2 receptor (pancreas)

Gi → ↓ insulin secretion

β2 receptor (pancreas)

Gs → ↑ glucagon secretion

SNS net glucose effect

↑ blood glucose (glucagon > insulin)

PNS pancreas effect

M3 (Gq) → ↑ insulin → ↓ blood glucose

Insulin (Humulin)

Agonist at insulin receptor → ↑ glucose uptake → treats diabetes

Glucagon (Baqsimi)

Glucagon receptor agonist → ↑ glycogenolysis → treats severe hypoglycemia

Somatostatin

↓ insulin and ↓ glucagon secretion

Bladder (PNS)

M3 agonism → contract detrusor + relax sphincter → urination

Bladder (SNS)

β2/β3 agonism relax detrusor; α1 agonism contracts sphincter → retention

Micturition reflex

Stretch receptors → spinal cord → PNS activation → urination

Metoclopramide

Sensitizes tissues to ACh → ↑ GI motility → treats GERD/gastroparesis

Dicyclomine

M3 antagonist → ↓ GI motility → treats IBS

Dicyclomine side effects

Anticholinergic: dry mouth, ↓ sweating, ↑ HR, pupil dilation

Digestion regulation

ENS, ANS, bacteria, serotonin, dopamine, NE, ACh (ALL correct)

Glycolysis

Glucose → pyruvate → ATP + NADH

Gluconeogenesis

New glucose from non-carbohydrate sources

Glycogenesis

Glucose → glycogen storage

Glycogenolysis

Glycogen → glucose

Chronic SNS activation pathway

SNS → ↑ glucagon → hyperglycemia → insulin resistance → inflammation → diabetes + heart disease

Exercise effect

↑ insulin sensitivity + restores SNS/PNS balance

COPD definition

Chronic inflammatory lung disease causing airflow limitation and obstruction (especially expiration)

COPD mechanism

Chronic inflammation → mucus buildup + airway narrowing → ↓ airflow

COPD emphysema component

Loss of elastic recoil → air trapping → impaired gas exchange

COPD key problem

Bronchoconstriction + obstruction of airflow

Smooth muscle (lungs)

Controls airway diameter via contraction/relaxation

Bronchoconstriction mechanism

M3 receptor activation → Gq → ↑ Ca2+ → contraction

Bronchodilation mechanism

β2 receptor activation → Gs → ↑ cAMP → relaxation

β2 receptor (lungs)

Activation → bronchodilation → improves airflow

M3 receptor (lungs)

Activation → bronchoconstriction → worsens COPD

Heart (SNS effect)

β1 activation → ↑ HR and ↑ contractility → ↑ cardiac output

Heart (PNS effect)

M2 activation → ↓ HR → ↓ cardiac output

Blood vessels (SNS α1)

Activation → vasoconstriction → ↑ BP

Blood vessels (SNS β2)

Activation → vasodilation → ↓ BP

Blood pressure equation

BP = CO × R

CO (cardiac output)

HR × stroke volume

Resistance (R)

Vessel diameter (vasoconstriction ↑ R, vasodilation ↓ R)

Hypertension mechanism

↑ peripheral resistance → ↑ BP

Hypotension mechanism

↓ CO or ↓ resistance → ↓ BP

β-blockers suffix

-olol

β-blockers mechanism

β1 antagonists → ↓ HR and ↓ contractility → ↓ BP

β-blockers use

Hypertension, heart disease, arrhythmias

Nonselective β-blockers

Block β1 and β2 receptors

β-blockers COPD risk

Block β2 → bronchoconstriction → worsens breathing

β1 selective blockers

Preferentially block β1 → less effect on lungs

Metoprolol

β1 antagonist → treats hypertension and heart disease

β2 agonists suffix

-erol

β2 agonist mechanism

β2 activation → ↑ cAMP → bronchodilation