RAAS Flashcards
This system invelved in pathophysiology of :
HTN, CHF, MI, diabetic nephropathy
It is a protese synthesized and stored in juxtaglomerular apparatus (JGA) of nephron that lie in the wall of the afferent arterioles
Renin
JGA is innervated by :
nor-adrenergic neurons
Control of renin by 3 pathways:
Two acting locally:1.macula densa and intra-renal baroreceptor
And one is CNS mediated by NE release from renal nor-adrenergic nerve.
Macula densa pathway
NaCl flux across the M.D inhibits renin release, and vise versa
Regulation of this pathway is more dependent on the luminal con. Of Na+ and Cl
PG and adenosin mediate this pathway
PG ++ renin release
Adenosin – renin release
Intra renal baroreceptor pathway:
++ pressure in the preglomerular vessele – renin release
— pressure in the preglomerular vessels stimulates renin release
CNS mediated pathway
By NE release from renal NA nerve
Stimulation of beta receptors on JGC increases renin secretion
Factors ++ renin release:
Loop diuretic, vasodilators, beta agonist, alpha antagonist phosphodiesterase inhibitors (-- c-AMP in JGC)
Factors – renin release:
NSAIDs》–PG
Beta blockers
Centrally acting sympatholytic drugs
Direct renin inhibitor:
Aliskiren
Mechanism of action of aliskiren:
It blocks the conversion of prorenin to renin
Angiotensinogen synthesized in :
In The Live
Factors that + Angiotensinogen sythesis:
Inflammation, insulin, estrogen, glucocorticoid, thyroid h, pregnancy and AgII
ACEs:
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Angiotensinase:
It metabolises AgII
the product has V.D effect
Does not hydrolyse bradykinin
It is not inhibited by ACE I
Angiotensin R
GPCR(q)
There is 2 subtypes
AT1-R:
+ PLC》IP3,DAG》S.M. contraction
Vascular and cardiac growth mediated by other pathway through tyrosine kinase pathway》+ transcription of some specifi genes
It is associated with HTN, hypertrophic cardiomyopathy, coronary artery disease
Most of AgII action is mediated via this receptor:
AT1-R
AT2-R:
Distributed widely in fetal tissue
Antiproliferative
Antihypertensive
Vasodilator effect through NO dependent mechanism, may involve bradykinin B2-R
Pharmacological effects of AgII :
TPR: direct V.C, +NE release from sympathetic outflow, -NE reuptake into nerve terminal
CNS: + ABP by + symp out flow
+ ADH, stimulation of thirst centre and increases water intake
AgII effects on adrenal cortex and kidney :
Agii acts on the Zona glomerulosa and causes release of aldosterol Kidney : Renal VC》-RBF》-GFR \+ proximal tubular Na+ reabsorbtion - renin secretion Enhance renal sympathetic tone Facilitate renal adrenergic transmission
Effects of Aldosterol
It acts on the principal cells (p-cells) which are present at last part of DCT and collecting duct
It causes Na+ retension, k+, H+ excretion
So increases BP
AgII Altered CV structure
Stimulation migration, proliferation, hypertrophy of vascular S.M, cardiac myocyte, + extracellular matrix prodoction
Leading to CV hypertrophy and morphological changes》remodelling
Cardiac remodeling
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