Intrarenal RAS in chronic kidney

Question 1

What secretes angiotensinogen?

Answer 1

Liver

Question 2

What does pro-renin bind to and induce?

Answer 2

MAS receptor causing vasodilation

Question 3

What is renin synthesis and secretion dependent on?

Answer 3

Integrity of connexins

Question 4

What are connexins?

Answer 4

Gap junction proteins in granular cells involved in cell-to-cell communication

Question 5

What 3 things trigger renin release?

Answer 5

Decrease in renal perfusion pressure
decrease in salt delivery to macula densa
sympathetic nerve stimulation via beta 1 adrenoreceptors

Question 6

What secretes renin?

Answer 6

Juxta glomerular cells of renal afferent arterioles

Question 7

What does ANGII binding to AT1 induce?

Answer 7

protein phosphorylation
cell proliferation
vasoconstriction
increased sodium reabsoption

Question 8

What does ANGII binding to AT2 induce?

Answer 8

protein dephosphorylation
anti-proliferation
vasodilation
diuresis/natriuresis

Question 9

What is the murine homologue to human AT1R?

Answer 9

AT1A

Question 10

What are 3 pieces evidence of an intrarenal RAS?

Answer 10

Absence of high renin or ANGII in hypertensive disease
ANGII conc. in renal tissues were higher that could be explained by equilibration with circulating ANGII
High ANGII in specific compartments within kidney indicating selective local regulation of intrarenal ANGII

Question 11

Where was ANGII conc. found to be higher?

Answer 11

Interstitial fluid and intratubular

Question 12

Where is angiotensinogen locally produced?

Answer 12

Proximal tubule cells (secretes directly into tubule)

Question 13

Where is ACE mainly associated to in the kidney?

Answer 13

Brush border of PTs

Question 14

Where has renin mRNA and protein been found in the kidneys?

Answer 14

CT and CD

Question 15

Is angiotensinogen filtered by the kidneys?

Answer 15

Yes

Question 16

During JG renin suppression what supports continued intrarenal ANGII formation?

Answer 16

Upregulated renin production in distal nephron -> could lead to amplification/maintenance of hypertensive state

Question 17

What are kidney diseases associated with?

Answer 17

activation of intarenal RAAS

Question 18

How can you tell if intrarenal RAAS os activated in diabetic patients?

Answer 18

high urinary Agt
increase in renal BF in response to ACE inhibitor or ANG receptor blockade despite low plasma renin activity

Question 19

What happen in mice without the AT1 receptor in PT when administered ANGII?

Answer 19

Systolic BPs were significantly lower compared to controls at baseline and when fef high or low NaCl diet

Question 20

Was the systemic RAAS functioning in the KO mice?

Answer 20

Yes as response to acute infusion of vasoconstrictors (ANGII and Epinephrine) was identical to control

Question 21

What happened to fluid reabsorption in the KO mice?

Answer 21

Reduced due to absence of PT AT1A receptors

Question 22

Was BP higher or lower in KO mice?

Answer 22

Lowered and NaCl balance was lower -> knocking out AT1 receptors in PT provides protection against hypertension

Question 23

What sodium transporter in the PT cells was reduced in the KO animals?

Answer 23

NHE3 (PT cells)
NaPi2

Question 24

Was NKCC2 in the thick ascending limb affected in KO mice?

Answer 24

No