Intrarenal RAS in chronic kidney Flashcards
What secretes angiotensinogen?
Liver
What does pro-renin bind to and induce?
MAS receptor causing vasodilation
What is renin synthesis and secretion dependent on?
Integrity of connexins
What are connexins?
Gap junction proteins in granular cells involved in cell-to-cell communication
What 3 things trigger renin release?
Decrease in renal perfusion pressure
decrease in salt delivery to macula densa
sympathetic nerve stimulation via beta 1 adrenoreceptors
What secretes renin?
Juxta glomerular cells of renal afferent arterioles
What does ANGII binding to AT1 induce?
protein phosphorylation
cell proliferation
vasoconstriction
increased sodium reabsoption
What does ANGII binding to AT2 induce?
protein dephosphorylation
anti-proliferation
vasodilation
diuresis/natriuresis
What is the murine homologue to human AT1R?
AT1A
What are 3 pieces evidence of an intrarenal RAS?
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
Where was ANGII conc. found to be higher?
Interstitial fluid and intratubular
Where is angiotensinogen locally produced?
Proximal tubule cells (secretes directly into tubule)
Where is ACE mainly associated to in the kidney?
Brush border of PTs
Where has renin mRNA and protein been found in the kidneys?
CT and CD
Is angiotensinogen filtered by the kidneys?
Yes
During JG renin suppression what supports continued intrarenal ANGII formation?
Upregulated renin production in distal nephron -> could lead to amplification/maintenance of hypertensive state
What are kidney diseases associated with?
activation of intarenal RAAS
How can you tell if intrarenal RAAS os activated in diabetic patients?
high urinary Agt
increase in renal BF in response to ACE inhibitor or ANG receptor blockade despite low plasma renin activity
What happen in mice without the AT1 receptor in PT when administered ANGII?
Systolic BPs were significantly lower compared to controls at baseline and when fef high or low NaCl diet
Was the systemic RAAS functioning in the KO mice?
Yes as response to acute infusion of vasoconstrictors (ANGII and Epinephrine) was identical to control
What happened to fluid reabsorption in the KO mice?
Reduced due to absence of PT AT1A receptors
Was BP higher or lower in KO mice?
Lowered and NaCl balance was lower -> knocking out AT1 receptors in PT provides protection against hypertension
What sodium transporter in the PT cells was reduced in the KO animals?
NHE3 (PT cells)
NaPi2
Was NKCC2 in the thick ascending limb affected in KO mice?
No
