Last edited: 9/14/2021

1. AUTOREGULATION
Renal | Autoregulation (updated) Medical Editor: Gerard Jude Loyola

OUTLINE (2) ↓BP

I) RENAL AUTOREGULATION
II) INTRINSIC MECHANISMS
III) EXTRINSIC MECHANISMS
IV) APPENDIX
V) REVIEW QUESTIONS
VI) REFERENCES

I) RENAL AUTOREGULATION
Ability of the kidney to modify the blood flow and urine
output
Figure 2. Myogenic mechanism during decreased blood
How?
pressure. Erratum: vasoconstriction* should be vasodilation
o Intrinsic mechanisms:
 Myogenic mechanism ↓BP → ↓GHP → ↓GFR
 Tubuloglomerular feedback o ↓BP = ↓urine = can cause kidney injury
o Extrinsic mechanisms: o How does the kidney prevent it?
 Sympathetic nervous system
(i) Mechanism:
 Renin-angiotensin-aldosterone-ADH system
(RAAS) ↓BP = ↓blood to the AA = ↓stretch on the AA
↓stretch → ↓Na+ enter in the smooth muscle cell → less
II) INTRINSIC MECHANISMS positive charge → ↓Ca2+ released by the sarcoplasmic
reticulum → ↓contraction = relaxation
(A) MYOGENIC MECHANISM Relaxation of the smooth muscle → vasodilation → ↑GBF
Myogenic = muscle of afferent arteriole → ↑volume and filtration → ↑GFR
Blood pressure is a surrogate of the glomerular
hydrostatic pressure Summary:
o Glomerular hydrostatic pressure (GHP): pressure ↑BP = ↑GFR
inside the capillaries exerted to push substances out o Counteracted by vasoconstriction of AA → ↓GFR
of the capillaries and into the Bowman’s capsule ↓BP = ↓GFR
o Counteracted by vasodilation of AA → ↑GFR
(1) ↑BP
(B) TUBULOGLOMERULAR FEEDBACK
This mechanism is sensitive to NaCl
o NaCl gets reabsorbed in the proximal convoluted
tubule (PCT)
(1) ↑BP

Figure 1. Myogenic mechanism during increased blood

pressure. AA – afferent arteriole, EA – efferent arteriole, BC –
Bowman’s capsule, PCT – proximal convoluted tubule
↑BP → ↑GHP → ↑GFR
o Higher glomerular filtration rate (GFR), more urine
Kidneys modulate the GFR so that it is not too excessive
making too much urine, or the blood pressure does not
remain too high causing injury on the glomerular
capillaries

(i) Mechanism:
Blood flows through the AA then to the EA
↑BP = more blood to the AA
o ↑BP exerts more ↑stretch → Na+ influx → makes the
inside of cell super positive → stimulates
sarcoplasmic reticulum to unload Ca2+ → ↑Ca2+ inside
the cell → ↑binding of actin and myosin →
↑contraction → vasoconstriction
o Na channels in the smooth muscle is sensitive to
Figure 3. Tubuloglomerular feedback mechanism on high blood
stretch pressures. MDC – Macula densa cells, DCT – distal convoluted
AA vasoconstricts → ↓glomerular blood flow (GBF) → tubule, LH – loop of Henley, JG cells – juxtoglomerular cells
↓filtered plasma and other substance (↓GFR)

AUTOREGULATION RENAL PHYSIOLOGY: Note #1. 1 of 4

 ↑BP = ↑GFR = ↑NaCl excretion into the kidney tubules III) EXTRINSIC MECHANISMS
When NaCl transporters in the PCT are saturated, NaCl
can escape and move to the LH and then to the DCT Kicks in when blood pressure is relatively low
where macula densa cells are found o These mechanisms are more involved in these
o Special NaCl sensors circumstances
o Release adenosine when it detects ↑NaCl
(A) SYMPATHETIC NERVOUS SYSTEM
Adenosine functions to:
o (1) vasoconstrict AA → ↓GBF → ↓GFR → ↓NaCl
being filtered
o (2) inhibit juxtaglomerular (JG) cells → ↓renin →
↓blood pressure
Remember:
Renin functions to increase blood pressure through a
complicated process.
(2) ↓BP

Figure 5. Action of sympathetic nervous system in

autoregulation. HR - heart rate, SV - stroke volume, CO -
cardiac output, EPI - epinephrine, NE - norepinephrine, AT II -
angiotensin II and SVR – systemic vascular resistance.
Erratum: SUR* instead of SVR
Stimulus: ↓↓↓SBP → MAP < 65 mmHg
o MAP (mean arterial pressure): measure of perfusion
o When MAP < 65 mmHg, kidney is not perfused; blood
flow is redirected to other “more important” organs
such as the heart, brain and muscles
Figure 4. Tuberoglomerular feedback mechanism on low blood
↓BP → ↓GFR → ↓urine output
pressures.
o ↓blood flow can cause kidney injury
↓BP = ↓GFR = ↓NaCl excretion into the kidney tubules o SNS do its best to increase blood flow
When macula densa cells detect ↓NaCl in DCT, they
release PGI2 and nitric oxide (NO) (1) Effects of the Sympathetic Nervous System
PGI2 and NO function to: ↓BP triggers baroreceptors → CN IX and CN X send
o (1) vasodilate the AA → ↑GBF → ↑GFR → ↑NaCl ↓signals to the medulla
filtered Medulla activates sympathetic nerve fibers in the thoracic
o (2) stimulate the JG cells → ↑renin → ↑BP part causing release of NE and epinephrine

Summary:
(i) Heart
↑BP = ↑GFR = ↑NaCl filtered NE and epinephrine act on the nodal system → ↑HR, ↑SV
o ↑NaCl detected by MD cells → release adenosine (due to ↑contractility) → ↑CO → ↑BP
→ vasoconstricts AA and inhibits JG cells to o To increase blood flow in the kidneys to avoid injury
release renin
NE and epi stimulate the β1 receptors in the nodal
↓BP = ↓GFR = ↓NaCl filtered system and contractile fibers → ↑HR and ↑SV,
o ↓NaCl detected by MD cells → release PGI2 and NO
respectively
→ vasodilates AA and stimulates JG cells to
release renin o Chronotropic: change in heart rate
o Ionotropic: change in contractility

(ii) Afferent and Efferent Arterioles

SNS release NE and EPI that act on the α1 receptors of
the AA and EA → vasoconstriction → ↓GBF → ↓GFR

YES, the goal is to increase the blood flow towards the

kidney BUT in sympathetic crisis, the SNS does not
respect the kidneys �

2 of 4 RENAL PHYSIOLOGY: Note #1. AUTOREGULATION

 (iii) Systemic Vessels Function: act on the DCT to make them permeable water
and Na+
NE and EPI act on the α1 receptors on the systemic o ↑Na+ and H2O → ↑BV → ↑BP
vessels → vasoconstriction of multiple vessels →
↑systemic vascular resistance (SVR) → ↑BP (iv) Vasoconstriction of EA and ↑GFR
(iv) Juxtoglomerular Cells Angiotensin II binds on the receptor on the EA →
vasoconstriction of EA
NE and EPI stimulate the β1 receptors on the JG cells → o Less blood can escape from the glomerulus, more
↑renin → activates angiotensin II →→→ ↑BP blood stays in the glomerulus → more blood filtered
out → ↑GFR
Effects of the Sympathetic Nervous System: o NOTE: Some books say that it also affects the AA;
Increase HR and SV
but the effect is much greater in EA (EA >>> AA)
Vasoconstriction of the afferent and efferent arterioles
Vasoconstriction of the systemic vessels → ↑SVR Angiotensin II act on the PCT to cause increased
Triggers release of renin reabsorption of Na+ and H2O
o ↑Na+ and H2O → ↑BV → ↑BP
The effects are the exact opposite when the blood
pressure is HIGH. (v) Vasoconstriction of Systemic Vessels
Angiotensin II act on systemic vessels → potent
(B) RENIN-ANGIOTENSIN-ALDOSTERONE-ADH AXIS vasoconstriction → ↑SVR → ↑BP → ↑GFR

In cases of ↑BP, JG cells do NOT release renin.

Therefore, this cascade does not occur.
(2) Atrial Natriuretic Peptide (ANP)
Released from the heart in cases of ↑BP (Figure 6)
Function: can block any function of the angiotensin II
o Blocks ADH release = no water and Na+ reabsorption
= urinate water and Na+ = ↓blood volume
o Blocks aldosterone release = no water and Na+
reabsorption = urinate water and Na+ = ↓blood
volume
o Prevents vasoconstriction of EA = ↓GFR
o Inhibits water and Na+ reabsorption = urinate water
and Na+ = ↓blood volume
o Vasodilation of blood vessels = ↓SVR = ↓BP

Figure 6. The renin-angiotensin-aldosterone-ADH axis.

Erratum: *SUR instead of SVR
↓BP → ↓GFR
Juxtoglomerular cells are sensitive to changes in blood
pressure
o When BP is low, JG cells release renin
Renin cleaves angiotensinogen to produce angiotensin I
Angiotensin I move to the capillaries in the lungs and get
converted to angiotensin II by angiotensin converting
enzyme (ACE)
(1) Functions of Angiotensin II

(i) ADH Release

Angiotensin II stimulates the hypothalamus that trigger
release of ADH from the pituitary gland
ADH
o Also called vasopressin or antidiuretic hormone
o Acts on the aquaporin in the collecting duct to
reabsorb water
 ↑H2O in blood → ↑blood volume → ↑BP

(ii) ↑Thirst
Makes you thirsty → ↑water intake → ↑blood volume →
↑BP

(iii) Aldosterone Release

Angiotensin II stimulates release of aldosterone from the
zona glomerulosa (ZG) in the adrenal gland

AUTOREGULATION RENAL PHYSIOLOGY: Note #1. 3 of 4

 IV) APPENDIX
Table 1. Summary of autoregulatory mechanisms of the kidneys.
INTRINSIC EXTRINSIC
Tubuloglomerular Sympathetic Nervous Renin-Angiotensin-
Myogenic Mechanism
Feedback System Aldosterone-ADH Axis
↓BP stimulates release of Renin cleaves
NE and EPI from medulla angiotensinogen to
Actions: angiotensin I → angiotensin
↑HR, ↑SV = ↑CO = ↑BP II (lungs)
↑BP = ↑GFR = ↑NaCl filtered Functions of Ang II
↑NaCl detected by MD cells o Through the
→ release adenosine → stimulation of the Release of ADH = ↑H2O
↑BP = ↑GFR vasoconstricts AA and nodal system and reabsorption = ↑BP
Counteracted by inhibits JG cells to release through β1 receptors Thirst = ↑water intake =
vasoconstriction of AA → renin Vasoconstriction of AE ↑BP
↓GFR ↓BP = ↓GFR = ↓NaCl filtered and EE through Release of aldosterone =
↓BP = ↓GFR ↓NaCl detected by MD cells stimulation of α1 ↑H2O and Na+
Counteracted by → release PGI2 and NO → receptors = ↓GFR reabsorption = ↑BP
vasodilation of AA → ↑GFR vasodilates AA and Vasoconstriction of Vasoconstriction of
stimulates JG cells to systemic vessels = ↑SVR efferent arterioles =
release renin = ↑BP ↑GFR
Stimulates renin release ↑Reabsorption of water
from JG cells and Na+ (PCT)
Vasoconstriction of
systemic vessels

V) REVIEW QUESTIONS VI) REFERENCES

1) All of the following functions of angiotensin II
increase the blood pressure EXCEPT:
a) Stimulation of the hypothalamus
b) Stimulation of the zona glomerulosa
c) Vasoconstriction of the efferent arterioles
d) Vasoconstriction of the systemic vessels
2) Which of the following is NOT an effect of the
sympathetic nervous system in increasing blood
pressure?
a) Stimulates β1 receptors in the nodal system and
contractile fibers
b) Stimulates the α1 receptors on the afferent and
efferent arterioles
c) Stimulates release of renin
d) Stimulates the α1 receptors on the general vascular
system
3) What stimulus is important in the tubuloglomerular
feedback?
a) O2
b) Stretch
c) NaCl
d) Baroreceptors
4) At low blood pressures, the macula densa cells
release what substances to counteract the change in
blood pressure?
a) Adenosine
b) NO2
c) PGI2
d) B & C
5) Myogenic mechanism takes advantage of what
stimulus?
a) Stretch of the afferent arteriole
b) Stretch of the efferent arteriole
c) Change in osmolarity
d) Change in osmolality

CHECK YOUR ANSWERS

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