Vascular Regulation & Neural Control

1. Only THREE mechanisms regulate blood flow

Everything in this chapter boils down to three levers:

(A) Cardiac output

– Heart pumps more or less blood.

(B) Arteriolar resistance (diameter)

– Main controller of tissue blood flow

– Determines systemic vascular resistance → BP

(C) Venous capacitance (vein diameter)

– Controls venous return → stroke volume → CO

⭐ If resistance ↑ → flow ↓, BP ↑

⭐ If veins constrict → venous return ↑ → CO ↑

2. Arterioles are the MAIN control point

Because:

• They have thick smooth muscle
• They create most of the resistance
• They respond to local, endothelial, neural, and hormonal signals

➡️ “Arterioles decide where blood should go.”

3. Local control = tissues regulate their own blood

This is 50% of exam questions.

Vasodilation (active tissues):

• ↑ CO₂
• ↓ O₂
• ↑ H⁺ (↓ pH)
• ↑ K⁺
• ↑ Adenosine
• ↑ Lactate
• ↑ Temperature

➡️ “Metabolic vasodilation” — active tissues get more blood.

Autoregulation:

Tissues keep their blood flow constant despite pressure changes.

(E.g., brain, kidney, heart)

4. Endothelium releases powerful vasoactive agents

Vasodilators (very high-yield):

• NO (nitric oxide) → relaxes smooth muscle
• Prostacyclin (PGI₂)
• Kinins (e.g., bradykinin)

Vasoconstrictors:

• Endothelin-1 ← strongest
• Platelet serotonin
• Thromboxane A₂

➡️ Exam trigger: “Endothelin = strongest vasoconstrictor”

5. Circulating hormones that affect arterioles

Vasoconstrictors (super-high yield):

• Norepinephrine
• Epinephrine (most tissues)
• Angiotensin II
• Vasopressin (ADH)
• Neuropeptide Y

Vasodilators:

• Epinephrine in skeletal muscle & liver (β2)
• Histamine
• ANP
• CGRP (calcitonin gene related peptide)
• VIP

➡️ Key point: Epinephrine = constricts everywhere EXCEPT muscle & liver (vasodilates via β2).

6. Neural control is almost 100% sympathetic

THIS is the biggest scoring point.

Arterioles:

• Sympathetic noradrenergic fibers
• ↑ Sympathetic discharge → vasoconstriction
• ↓ Sympathetic discharge → vasodilation

→ Parasympathetic rarely innervates blood vessels

(but exceptions = erectile tissue, uterine, facial, salivary)

Skeletal muscle “vasodilator fibers”?

Humans: NO TRUE sympathetic cholinergic vasodilator system

Vasodilation here is due to epinephrine (β2).

7. Veins also receive sympathetic innervation

• Veins = capacitance vessels
• Sympathetic stimulation → venoconstriction

→ ↑ Venous return → ↑ Stroke volume → ↑ Cardiac output

➡️ Splanchnic veins have the densest innervation.

8. Sympathectomy = vessels dilate

Why?

→ Loss of baseline sympathetic tone (vasoconstrictor tone).

This proves:

Sympathetic tone keeps arterioles partially constricted at rest.

9. The emergency rule: protect heart & brain

In hemorrhage:

• Arterioles in skin, muscle, gut constrict
• Blood is diverted to brain + heart
• Veins constrict → push blood centrally

⭐ THE CORE IDEA (if you understand this, you aced the chapter)

Blood vessels are normally kept in a partially constricted state by sympathetic tone.

Local metabolic factors override this at the tissue level.

Endothelium fine-tunes it.

Hormones make global adjustments.

➡️ Local = Priority

➡️ Neural = System-wide control

➡️ Humoral = Backup + reinforcement

Autonomic Innervation of the Heart

1. The heart receives BOTH sympathetic and parasympathetic inputs

This is the opposite of blood vessels.

✔ Sympathetic (β₁ receptors):

• SA node → ↑ heart rate (positive chronotropy)
• AV node → ↑ conduction velocity (positive dromotropy)
• Ventricles → ↑ contractility (positive inotropy)
• His-Purkinje → ↑ conduction

Neurotransmitter: norepinephrine

Outcome: faster, stronger, more conductive heart.

✔ Parasympathetic (vagus, M receptors):

• SA node → ↓ heart rate
• AV node → ↓ conduction
• Atria → ↓ contractility (ventricular effect minimal)

Neurotransmitter: acetylcholine

Outcome: slows and calms the heart.

2. Parasympathetic effects dominate at rest (vagal tone)

This is the highest-yield concept.

At rest:

• Vagus is active
• Sympathetic is moderately active

Because of vagal tone:

• Resting HR ≈ 70 bpm

Remove vagal tone → HR jumps to 150–180 bpm after atropine.

3. Intrinsic heart rate (no autonomic influence)

If BOTH systems are blocked:

• HR ≈ 100 bpm

This proves:

• Vagus slows HR from 100 → 70
• Sympathetic pushes HR upward from 100 → higher

4. Cross-talk between nerves enhances effects

Highly examinable:

• ACh released from vagus inhibits NE release from sympathetic terminals

→ Parasympathetic effects become even stronger.

This is why a small vagal burst can rapidly slow the heart.

5. The real “story” examiners want

The heart:

• Speeds up and strengthens via sympathetic β₁ receptors
• Slows and dampens via vagal muscarinic receptors
• Is kept at 70 bpm mainly by vagal tone
• Would beat at 100 bpm with no autonomic control
• Jumps to 150–180 bpm with vagal block (atropine) because sympathetic tone becomes unopposed

⭐ THE 10 ONE-LINERS TO SCORE 80%

1. Sympathetic (β₁) increases HR, conduction, and contractility.
2. Parasympathetic (M₂) decreases HR and AV conduction.
3. Vagal tone dominates at rest → HR ≈ 70 bpm.
4. Sympathetic tone at rest is moderate.
5. Intrinsic HR without nerves = 100 bpm.
6. Atropine removes vagal tone → HR → 150–180 bpm.
7. Vagus slows the heart mainly via SA and AV nodes.
8. Sympathetic nerves act on SA, AV, His-Purkinje, ventricles.
9. ACh inhibits NE release → enhances vagal effect.
10. Parasympathetic effect on ventricles is weak (mostly atria).

Cardiovascular Control (Brainstem + Reflexes)

1. ONE CENTRAL CONTROLLER RUNS BLOOD PRESSURE: THE RVLM

The rostral ventrolateral medulla (RVLM) is the main driver of sympathetic tone.

RVLM:

• Sends excitatory signals ↓ spinal cord → preganglionic sympathetic neurons (IML)
• Maintains baseline vasoconstriction (sympathetic tone)
• Controls arterioles, veins, and heart
• Uses glutamate as neurotransmitter
• PNMT present but glutamate is the transmitter
• Overactivity → hypertension (even clinical cases from compression)

➡️ If RVLM fires more → BP ↑

➡️ If RVLM inhibited → BP ↓

This is the single most important point.

2. BARORECEPTORS: NEGATIVE FEEDBACK LOOP FOR BP

Rise in BP → ↑ baroreceptor firing → inhibits RVLM → ↓ sympathetic outflow →

• Vasodilation
• ↓ HR
• ↓ contractility
• ↑ venous pooling

Opposite occurs when BP falls.

➡️ Baroreceptors = fast BP stabilizers

➡️ RVLM = main sympathetic command center

3. Sympathetic and vagal outputs move in opposite directions

• ↑ Sympathetic → ↓ Vagal
• ↓ Sympathetic → ↑ Vagal

This happens automatically via brainstem circuits.

➡️ Heart rate = balance of sympathetic vs vagus.

4. Veins also constrict with sympathetic activation

• ↑ Sympathetic → venoconstriction → ↑ venous return → ↑ stroke volume

Important because veins hold 70% of blood volume.

5. MANY INPUTS MODIFY RVLM ACTIVITY

Everything below acts via the RVLM unless stated otherwise:

Increases BP (↑ RVLM firing):

• Pain (brief)
• Exercise (muscle afferents)
• Stress, fear, anger (via hypothalamus)
• Somatosympathetic reflex (touch, stimulation of skin/muscle afferents)

Decreases BP (↓ RVLM firing):

• Lung inflation (via vagal stretch receptors)
• Baroreceptors
• Some prolonged pain (can → fainting)

➡️ “RVLM’s job = integrate all signals → set sympathetic output.”

6. Hypothalamus + cortex modulate cardiovascular responses

• Limbic cortex → emotional BP changes
• Hypothalamus → relays these to RVLM
• RVLM sends final sympathetic commands to vessels & heart

➡️ This explains:

• Stress-induced tachycardia
• “White coat hypertension”
• Sexual excitement BP rise

7. Cardiac vagal control originates in the nucleus ambiguus

• Nucleus ambiguus → parasympathetic (vagal) output to SA & AV nodes
• Usually inhibited when sympathetic tone rises
• Activated when BP falls (via baroreflex)

8. Heart rate changes usually parallel BP changes, BUT NOT ALWAYS

HIGH-YIELD exceptions:

Atrial stretch receptors

• → BP falls (vasodilation)
• → HR rises (tachycardia)

Raised intracranial pressure (Cushing reflex)

• → BP rises
• → HR falls (bradycardia)

→ Important MCQ traps.

BARORECEPTORS

1. Baroreceptors = stretch sensors for BP control

They are mechanoreceptors that fire more when vessels stretch (↑ BP) and fire less when vessels relax (↓ BP).

2. Two types of baroreceptors

A. High-pressure baroreceptors

Monitor arterial BP

Located in:

• Carotid sinus (internal carotid just above bifurcation)
• Aortic arch

B. Low-pressure baroreceptors (cardiopulmonary)

Monitor blood volume

Located in:

• Right & left atria
• SVC & IVC entry
• Pulmonary veins
• Pulmonary circulation

➡️ High-pressure = BP

➡️ Low-pressure = circulating volume

3. Afferent pathways (VERY high yield)

Rigid favourite of examiners.

4. The central pathway (the real “gold” the exam wants)

Step 1 — Afferents → NTS

All baroreceptor signals go to the

➡️ Nucleus tractus solitarius (NTS)

Neurotransmitter: glutamate

Step 2 — NTS → CVLM

NTS excites:

➡️ CVLM (glutamate)

CVLM inhibits:

➡️ RVLM (GABA)

Step 3 — RVLM ↓ → less sympathetic tone

→ Vasodilation

→ Venodilation

→ ↓ HR

→ ↓ contractility

→ ↓ BP

→ ↓ venous return

Step 4 — NTS → Nucleus ambiguus (vagal motor nuclei)

→ ↑ Vagal output to SA & AV nodes

→ Bradycardia

⭐ THUS: Increased BP → ↑ baroreceptor firing → ↓ sympathetic + ↑ vagal → ↓ BP.

This is the entire reflex.

5. What happens when baroreceptors fire more?

Effects (very high yield):

• ↓ Sympathetic → vasodilation
• ↓ Sympathetic → venodilation
• ↓ Sympathetic → ↓ heart contractility
• ↑ Vagal → bradycardia
• ↓ Cardiac output
• ↓ BP

➡️ This is the fastest BP-stabilizing reflex in the body.

⭐ 10 ONE-LINERS to SCORE 80%

1. Carotid sinus via CN IX; Aortic arch via CN X.
2. Both send glutamatergic signals to NTS in medulla.
3. NTS → CVLM (excite) → RVLM (inhibit) → ↓ sympathetic tone.
4. NTS directly excites vagal motor nuclei → ↑ vagal output.
5. High BP → ↑ firing → reflex ↓ BP (classic negative feedback).
6. Vasodilation + venodilation = ↓ pressure + ↑ blood pooling.
7. Bradycardia = key vagal response.
8. Reduced RVLM = reduced systemic vasoconstriction.
9. Low-pressure receptors sense volume, not pressure.
10. Baroreflex is rapid — seconds, not minutes.

✅ Baroreceptor Firing, Resetting & RVLM Control

1. Baroreceptors respond BEST to pulsatile pressure

This is the SINGLE most important detail.

⭐ Key idea:

A rising + falling pressure (pulsatile) stretches receptors more → more firing. Constant pressure stretches less → less firing.

➡️ Pulse pressure ↓ = firing ↓ = reflex ↑ BP + tachycardia

(Even if mean BP unchanged.)

This is a common MCQ trap.

2. Firing pattern depends on mean BP

At normal BP (~100 mmHg):

• Firing mostly during systole
• Few impulses during early diastole

At low BP:

• Firing only in systole

→ overall firing rate drops sharply

At high BP:

• Firing throughout the cardiac cycle

➡️ Firing increases from 50 → max at ~200 mmHg

3. Thresholds (VERY high yield numbers)

➡️ The reflex is strongest in the 70–110 mmHg range.

4. Full reflex logic (1 line):

↑ BP → ↑ Stretch → ↑ Baroreceptor firing →

NTS → CVLM → ↓ RVLM → ↓ Sympathetic + ↑ Vagal → ↓ BP, ↓ HR, ↓ CO

Reverse for ↓ BP.

➡️ This is the body's fastest BP-stabilizing system.

5. Baroreceptors stabilize BP BEAT-TO-BEAT

Any fall in BP reduces firing → increases sympathetic → increases HR + SV + vasoconstriction.

Any rise in BP increases firing → decreases sympathetic → decreases HR + CO + vasodilation.

➡️ Negative feedback loop for rapid BP control.

6. Baroreceptor resetting (VERY high yield)

Chronic hypertension:

• Baroreceptors reset upward to defend the new high BP.
• They now consider high BP as “normal.”
• Reflex still works, but around a higher set point.

Resetting is:

• Rapid
• Reversible

➡️ This is why baroreceptors cannot cure hypertension.

7. RVLM = main sympathetic command center

Factors increasing RVLM activity → ↑ BP:

• CO₂
• Hypoxia
• Pain (short-term)
• Stress, anger (via hypothalamus)
• Exercise (muscle afferents)
• Somatosympathetic reflex
• Chemoreceptors

Factors inhibiting RVLM → ↓ BP:

• Baroreceptors (major)
• Lung inflation
• CVLM
• Raphe nuclei
• Some cortical pathways

➡️ RVLM is the “final common pathway” for sympathetic BP control.

8. Clinical HIGH-YIELD: Neurovascular compression of RVLM

• Tumors (schwannoma, meningioma) or arteries compressing RVLM → ↑ sympathetic tone → hypertension.
• Decompression surgery sometimes lowers BP.

➡️ Essential hypertension may be partly neurogenic in some people.

9. Factors that increase vs decrease heart rate

(These come EXAM DIRECTLY.)

HR increases (tachycardia):

• ↓ Arterial baroreceptor activity
• ↑ Atrial stretch receptor activity
• Inspiration (normal physiology)
• Excitement, anger
• Most pain
• Hypoxia
• Exercise
• Thyroid hormones
• Fever

HR decreases (bradycardia):

• ↑ Arterial baroreceptor activity
• Expiration
• Fear, grief
• Trigeminal pain (diving reflex)
• ↑ Intracranial pressure (Cushing reflex)

➡️ Inspiration → HR ↑ ; Expiration → HR ↓

(Respiratory sinus arrhythmia — physiological)

⭐ TOP 10 HIGH-YIELD SENTENCES TO SCORE 80%

1. Baroreceptors respond more to pulsatile pressure than constant pressure.
2. Decreased pulse pressure → ↓ firing → tachycardia + ↑ BP.
3. Carotid sinus threshold ≈ 50 mmHg; max firing ≈ 200 mmHg.
4. Reflex strongest from 70–110 mmHg.
5. ↑ Baroreceptor firing → ↓ RVLM → ↓ sympathetic + ↑ vagal.
6. Baroreflex stabilizes BP every beat.
7. Chronic hypertension resets baroreceptors upward.
8. RVLM controls basal sympathetic tone; overactivity → hypertension.
9. Neurovascular compression of RVLM can cause essential hypertension.
10. HR increases with inspiration, hypoxia, ↓ baroreceptor activity; HR decreases with expiration, ↑ ICP, ↑ baroreceptor activity.

⭐ Baroreceptor & Chemoreceptor Control of BP

1. Baroreceptors = SHORT-TERM BP control

Location: Carotid sinus + Aortic arch

Stimulus: Stretch (↑BP → ↑firing)

What they do

• ↑ BP → ↑ baroreceptor firing → ↓ sympathetic, ↑ vagal → ↓ HR, ↓ BP
• ↓ BP → ↓ firing → ↑ sympathetic → ↑ HR, ↑ vasoconstriction, ↑ BP

Why high-yield?

Because:

➡ Postural changes

➡ Acute blood loss

➡ Exercise

➡ Phenylephrine test

➡ Valsalva maneuver

All rely on this reflex.

2. Resetting in Chronic Hypertension

• Baroreceptors adapt to high pressure → “reset” to a new high BP.
• So they defend the high BP instead of reducing it.
• Resetting is quick and reversible.

Exam punchline:

➡ Baroreceptors do NOT regulate long-term BP (kidney does).

3. Valsalva Maneuver: 4 Phases (SUPER HIGH-YIELD)

Phase I: Start straining → ↑ intrathoracic pressure → BP ↑ briefly

Phase II: Venous return ↓ → CO ↓ → BP ↓ → reflex tachycardia

Phase III: Release strain → intrathoracic pressure normalizes → BP dips

Phase IV: CO restored but vessels still constricted → BP overshoots, bradycardia

KEY exam line:

➡ Sympathetic lesions → no BP overshoot

➡ Autonomic failure → no HR compensation

4. Atrial Stretch Receptors

Two types:

Type A → fires in atrial systole

Type B → fires in atrial filling

Increased venous return → more type B firing → Bainbridge reflex = ↑HR

Why important?

➡ Explains why ↑ venous return does NOT slow HR (opposite to arterial baroreceptors).

5. Ventricular Receptors

• Activated by ventricular distension
• Cause vagal bradycardia + hypotension
• Maintain resting vagal tone

Clinical:

➡ Overdistension (ischemia, infarction) → Bezold–Jarisch reflex (bradycardia, hypotension, apnea)

6. Peripheral Chemoreceptors (Carotid & Aortic bodies)

Stimuli:

• ↓O₂ (main)
• ↑CO₂
• ↓pH

Effects:

• ↑ sympathetic → vasoconstriction
• HR effect depends on respiration (hyperventilation causes tachycardia)

Key point:

➡ Hypoxia strongly stimulates ventilation → this dominates HR response.

7. Mayer Waves vs Traube–Hering Waves

➡ Traube–Hering = BP oscillations with respiration

➡ Mayer = slow oscillations (one every 20–40 sec) during hypotension, due to chemoreceptor cycling

8. Central Chemoreceptors & Cushing Reflex

Raised intracranial pressure (ICP) → ↓ blood flow to medulla → local hypercapnia & hypoxia → RVLM activation → massive sympathetic discharge → severe hypertension

→ Baroreceptors respond → reflex bradycardia

Clinical triad: Cushing reflex

• ↑ BP
• ↓ HR
• irregular breathing

This is very high-yield.

9. Hypercapnia: Peripheral vs Central

• Central effect of CO₂ = vasoconstriction + ↑ BP
• Peripheral effect = vasodilation

➡ They partially cancel each other.

⭐ SUPER HIGH-YIELD SUMMARY TABLE (Last-minute revision)

⭐ LOCAL REGULATION OF BLOOD FLOW

1. Autoregulation = Tissue controls its own blood flow (short-term local control)

Most vital organs do this: Kidney, Brain, Heart, Skeletal muscle, Mesentery, Liver.

Definition (must memorize):

Tissue keeps blood flow constant despite changes in perfusion pressure.

How?

Two main mechanisms:

A. Myogenic Theory (stretch → constrict)

• ↑ Pressure → vessel wall stretches
• Smooth muscle contracts → vessel narrows
• Flow stays constant

Think: “Stretch → Squeeze”

Law of Laplace:

Tension = Pressure × Radius

To keep tension constant when pressure rises → radius must fall → vessel constricts.

B. Metabolic Theory (↓Flow → metabolites accumulate → dilation)

When tissue is active or blood flow drops:

• ↓O₂
• ↓pH
• ↑CO₂
• ↑K⁺
• ↑Osmolality
• ↑Temperature
• ↑Lactate

These cause local vasodilation → more blood flow.

KEY EXAM LINE:

➡ Low O₂ → HIF-1α activation → vasodilatory gene expression.

Remember:

Metabolites get washed away when flow increases → vasodilation stops.

⭐ 2. Vasodilator Metabolites (super high yield)

These ALWAYS cause LOCAL vasodilation:

Major metabolic vasodilators:

• ↓O₂ → strongest trigger
• ↑CO₂
• ↓pH (acidosis)
• ↑K⁺
• ↑Osmolality
• ↑Temperature
• Lactate

Special cases:

• Adenosine → important vasodilator in cardiac muscle
• Histamine → from damaged tissues → ↑capillary permeability (swelling)
• Adenosine also inhibits noradrenaline release (local anti-sympathetic)

Brain: CO₂ is a powerful dilator

Skin: CO₂ also strongly dilates

⭐ 3. Local Vasoconstriction (must know)

Some stimuli cause local constriction independent of nerves:

A. Injury to vessels

• Platelets release serotonin (5-HT) → intense vasoconstriction

➡ Explains why cut vessels initially constrict.

B. Cold exposure

• Local cold → vasoconstriction

➡ Helps conserve heat (thermoregulation).

C. Injured veins also constrict

Not just arteries.

⭐ 4. What exams love to ask (golden points)

✔ Autoregulation is strongest in: Kidney > Brain > Heart

✔ Myogenic = response to pressure

✔ Metabolic = response to flow/tissue activity

✔ Low O₂ → strongest metabolic vasodilator

✔ HIF-1α activated by hypoxia → vasodilatory gene program

✔ CO₂ dilates brain vessels strongly

✔ Adenosine – vasodilator in heart

✔ Serotonin → vasoconstriction in injured vessels

✔ Cold → vasoconstriction

✔ Histamine → vasodilation + ↑ capillary permeability in inflammation

If you know these 10 lines → full marks.

⭐ Super-Simple Summary (Last-Minute Revision)

⭐ ENDOTHELIAL SECRETIONS

1. Prostacyclin vs Thromboxane A₂ (exam gold)

Why this is high-yield

• They balance each other → localized clotting without blocking flow.
• Aspirin shifts balance toward prostacyclin → anti-thrombotic effect.

Aspirin mechanism (must know)

• Irreversibly inhibits cyclooxygenase (COX).
• Endothelium regenerates COX quickly (hours).
• Platelets cannot regenerate COX (life = 7–10 days).

➡ Net effect: ↓ TXA₂ > ↓ PGI₂ → less clotting

➡ Prevents: MI, unstable angina, TIA, stroke.

⭐ 2. Nitric Oxide (NO): Most important vasodilator

Source

• Endothelium via NOS-3 (endothelial NOS)
• Made from arginine → citrulline

Stimuli that cause NO release

• Acetylcholine
• Bradykinin
• Histamine (H1)
• Shear stress (flow increases)
• Platelet products

Mechanism

1. Endothelium releases NO
2. NO diffuses to smooth muscle
3. Activates guanylyl cyclase
4. ↑ cGMP
5. Vasodilation

Why massively high-yield

• NOS-3 knockout mice → hypertension → proves tonic NO maintains BP.
• Nitroglycerin works like NO (↑ cGMP) → angina treatment.
• Viagra → inhibits cGMP breakdown → enhances NO action → erection.

Endothelium-dependent vs independent dilation

• Endothelium-dependent: ACh, histamine (H1), bradykinin, VIP, substance P
• Endothelium-independent: ANP, adenosine, histamine (H2)

⭐ 3. Endothelin-1 (ET-1): Most powerful vasoconstrictor

Source

• Endothelial cells (local/paracrine)

Activation

• Gene → Big endothelin (inactive) → ET-1 via endothelin-converting enzyme

Receptors

• ETA → vasoconstriction
• ETB → vasodilation or developmental signaling

Regulation high-yield

Stimulators of ET-1:

• Angiotensin II
• Catecholamines
• Growth factors
• Hypoxia
• Thrombin
• Shear stress
• Insulin
• Oxidized LDL

Inhibitors:

• NO
• ANP
• Prostacyclin
• PGE₂

🧠 Think balance:

NO & Prostacyclin = vasodilation

ET-1 = vasoconstriction

Clinical pearls

• ET-1 ↑ in heart failure & post-MI
• NOT increased in essential hypertension
• Important in ductus arteriosus closure at birth
• ET-1 knockout → facial defects + Hirschsprung disease

⭐ 4. Carbon Monoxide (CO) & Hydrogen Sulfide (H₂S)

Not exam heavy but good to know.

CO

• Generated by heme oxygenase (HO-2)
• Causes local vasodilation
• Works similar to NO but weaker

H₂S

• Emerging vasodilator gas
• Role still being defined

⭐ 5. Why endothelium is a MAJOR vascular organ

Endothelium secretes:

• Prostacyclin (PGI₂) → vasodilation
• NO → vasodilation
• Endothelin-1 → vasoconstriction
• Growth factors
• Antithrombotic + prothrombotic substances

➡ Controls vascular tone, clotting, inflammation, angiogenesis, BP regulation.

⭐ SUPER HIGH-YIELD CONTRAST TABLE (Exam Favorite)

⭐ The 10 exam lines you must remember

1. Prostacyclin = vasodilation + anti-platelet.
2. Thromboxane = vasoconstriction + pro-platelet.
3. Aspirin → ↓ TXA₂ (more) than PGI₂ → anti-thrombotic.
4. NO = major vasodilator → cGMP pathway.
5. ACh and bradykinin cause dilation via NO, not directly on smooth muscle.
6. NOS-3 knockout → hypertension (NO maintains tonic vasodilation).
7. Nitroglycerin acts like NO (↑ cGMP).
8. Viagra inhibits cGMP breakdown → prolongs NO action.
9. Endothelin-1 = most potent vasoconstrictor.
10. Endothelin stimulated by: Ang II, catecholamines, hypoxia, thrombin. Inhibited by: NO, ANP, prostacyclin.

Learn these → Full marks.

⭐ Neurohumoral Regulation of Vascular Tone

1. Kinins (Bradykinin & Kallidin) — High-Yield Vasodilators

What they are

• Bradykinin (nonapeptide)
• Kallidin = lysyl-bradykinin (decapeptide)

Both → powerful vasodilators (via NO).

How they are formed

• Origin from kininogens (HMWK & LMWK)
• Kallikreins release kinins from precursors
• Plasma prekallikrein activated by Factor XII → kallikrein
• This links kinins to clotting.

How they are broken down

• Kininase I → partial activation
• Kininase II = ACE → inactivates bradykinin (VERY IMPORTANT)

➡ ACE inhibitors ↑ bradykinin → cough + angioedema

Main effects of kinins (must know)

• Vasodilation (NO-mediated) → ↓ BP
• ↑ vascular permeability → edema
• Pain
• Attract leukocytes
• Smooth muscle contraction (visceral)

Clinical pearl

• C1-esterase inhibitor deficiency → hereditary angioedema (bradykinin-mediated)

⭐ 2. Natriuretic Peptides (ANP, BNP, CNP)

When released

• Hypervolemia / stretch

Main actions

• Vasodilation
• Natriuresis (kidney)
• Antagonize: Angiotensin II, Aldosterone, Vasopressin

Exam rule

• ANP & BNP circulate
• CNP = paracrine (local)

Why important

• ANP/BNP link vascular tone ↔ kidney fluid balance
• BNP is a diagnostic marker in heart failure

⭐ 3. Major Circulating Vasoconstrictors (Very High Yield)

A. Vasopressin (ADH)

• Strong vasoconstrictor
• BUT → reflex ↓ cardiac output keeps BP change small
• More important in shock than normal physiology

B. Norepinephrine

• Generalized vasoconstriction (α1 receptors)

Important:

Circulating NE is less important than sympathetic nerve NE.

C. Epinephrine

• Vasodilation in skeletal muscle & liver (β2)
• Vasoconstriction elsewhere (α1)

Exam line:

Epinephrine redistributes blood to skeletal muscle during exercise.

D. Angiotensin II (the king of constriction)

• Very potent vasoconstrictor
• Formed via → Renin → Ang I → ACE → Ang II

Functions

• Maintains BP & ECF volume
• ↑ Aldosterone
• ↑ Thirst
• ↑ Vasoconstriction
• Local Renin-Ang systems may exist in vessel walls → role in hypertension

Clinical pearl

• ACE inhibitors ↓ Ang II
• Also ↑ bradykinin (because ACE = kininase II)

➡ Causes vasodilation, cough, angioedema

E. Urotensin-II

• One of the most potent vasoconstrictors
• ↑ in hypertension & heart failure

⭐ 4. SUPER-HIGH-YIELD QUICK TABLE (Memorize This)

⭐ 5. The 10 Exam Lines You MUST Know

1. Bradykinin = NO-mediated vasodilation + pain + increased permeability.
2. Kinins are broken down by ACE → ACE inhibitors ↑ bradykinin.
3. C1-esterase inhibitor deficiency → hereditary angioedema (bradykinin-mediated).
4. ANP/BNP released due to hypervolemia → vasodilation + natriuresis.
5. CNP is paracrine, ANP/BNP are endocrine.
6. Norepinephrine = generalized vasoconstriction (α1).
7. Epinephrine dilates muscle/liver (β2) but constricts elsewhere (α1).
8. Angiotensin II = key long-term vasoconstrictor + stimulates aldosterone & thirst.
9. ACE inhibitors block Ang II AND increase bradykinin.
10. Urotensin-II = potent vasoconstrictor; elevated in HTN & heart failure.