DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

A
Vasodilators
NaCl
Reabsorption
by
Proximal
Tubule
(–)
Diuretics
Pressure Natriuresis
ARTERIAL
BLOOD
PRESSURE
(+)
(–)
(–)
High
Pressure
Baroreceptors
Tubular
Delivery of
NaCl to MB
Renal
Sympathetic
Tone
(+)
(+)
(+)
Circulating
NE/Epi
MACULA DENSA (MD) PATHWAY
NaCl Reabsorption
at
Macula Densa
Loop
Diuretics
(–)
Blood Pressure
in
Pre-glomerular Vessels
Activation of
β 1 Adrenergic
Receptors on JGCs
Centrally Acting
Sympatholytics
(–)
(?)
INTRARENAL BARORECEPTOR PATHWAY
β ADRENERGIC RECEPTOR PATHWAY
(+)
LONG LOOP NEGATIVE FEEDBACK
(?)
β
Blockers
(–) PGI 2 /PGE 2 (–)
(–)
(–)
RENIN
RELEASE
(+)
(+)
(–)
Activation
of AT 1 R
NSAIDs
SHORT
LOOP
NEGATIVE
FEEDBACK
(+)
(–)
Ang II
Formation
AT 1
Blockers
(+)
Renin
Inhibitors
(–)
ACE
Inhibitors
Pharmacological Interventions
Physiological interrelationships
Major pathways modulating renin release
723
CHAPTER 26
B
Macula densa
Na + Na + Na +
P2Y-R
Juxtoglomerular cell
ATP
2Cl – 2Cl –
A 1
-R
K + K + G i
ADP
AC
G q
PLC
G q
*nNOS
–
AT 1 -R
+
ADO
cAMP Ca2+
–
PG-Rs
NO
+ + –
G s
+
PGs
AC
Renin
*COX-2 β 1
-R
G s
ATP
AngII
RENIN AND ANGIOTENSIN
*Expression upregulated
by chronic Na + depletion
Catecholamines
Circulating
renin
Figure 26–2. A. Schematic portrayal of the three major physiological pathways regulating renin release. See text for details. MD,
macula densa; PGI 2
/PGE 2
prostaglandins I 2
and E 2
; NSAIDs, nonsteroidal antiinflammatory drugs; Ang II, angiotensin II: ACE,
angiotensin-converting enzyme. AT 1
R, angiotensin subtype 1 receptor; NE/Epi, norepinephrine/epinephrine; JGCs, juxtaglomerular
cells. B. Mechanisms by which the macula densa regulates renin release. Changes in tubular delivery of NaCl to the macula densa
cause appropriate signals to be conveyed to the juxtaglomerular cells. Sodium depletion upregulates nNOS and COX-2 in the macula
densa to enhance production of prostaglandins (PGs). PGs and catecholamines stimulate cyclic AMP production and thence renin
release from the juxtaglomerular cells. Increased NaCl transport depletes ATP and increases adenosine (ADO) levels. Adenosine diffuses
to the juxtaglomerular cells and inhibits cyclic AMP production and renin release via G i
-coupled A 1
receptors. Increased NaCl
transport in the macula densa augments the efflux of ATP, which may inhibit renin release directly by binding to P2Y receptors and
activating the G q
-PLC-IP 3
-Ca 2+ pathway in juxtaglomerular cells. Circulating AngII also inhibits renin release on juxtaglomerular
cells via G q
-coupled AT 1
receptors.