Pharm Block 2- Renin-Angiotensin System

Front 1

anatomy of the juxtaglomerular apparatus

Back 1

-JG cell (modified smooth m with renin granules)
-macula densa (epith cells sense Na)
-sympathetic nerves (media or afferent arteriole)

Front 2

juxtaglomerular cell

Back 2

-modified smooth muscle cell
-found in media of afferent arteriole
-contain renin granules

Front 3

macula densa

Back 3

-specialized epith cells
-found at point where distal tubule comes in contact with afferent arteriole

Front 4

renin

Back 4

-acid protease
-splits leu-leu bond of angiotensinogen to give angiotensin I
-isorenins found in brain, blood, vessels, uterus, etc

Front 5

angiotensinogen

Back 5

-a2 globulin
-synthesized by the liver
-amino-terminal sequence contains angiotensin I

Front 6

angiotensin I

Back 6

-decapeptide
-biologically inactive

Front 7

ACE

Back 7

-removes C-terminal His-Leu dipeptide from angI producing angII
-vascular endothelium, lung, kidney, plasma
-inactivates bradykinin

Front 8

angiotensin II

Back 8

-octapeptide
-biologically active
-t1/2=4min

Front 9

angiotensinases

Back 9

-nonspecific aminopeptidases and carboxypeptidases
-inactivate angI and angII

Front 10

aldosterone

Back 10

-mineralocorticoid
-acts on distal tubule and CD
-enhances Na reabsorption and K excretion
-synth by zona glomerulosa in adrenal cortex

Front 11

what stimulates synthesis of aldosterone

Back 11

-K+
-ACTH
-angII

Front 12

what the rate limiting step in the activation of the renin-angio system?

Back 12

-control of renin release

Front 13

what controls renin release?

Back 13

-intrarenal baroreceptors
-macula densa
-renal symp NS
-angiotensin II

Front 14

intrarenal baroreceptors and renin release

Back 14

-sense change in wall tension of afferent arteriole
-wall tension is inversely related to renin release

Front 15

macula densa and renin release

Back 15

-sense changes in Na load (UV) at distal tubule
-sodium load is inversely related to renin release

Front 16

renal symp NS and renin release

Back 16

-mediated by B1 receptors on JG cells
-renin release is increased by direct or indirect activation of renal symp nerves/b agonists

Front 17

angiotensin II and renin release

Back 17

-shortloop feedback
-suppresses renin release by direct action on JG cells
-AT1 rec antagonists and ACE inhibitors stim renin release

Front 18

mech of angII

Back 18

-specific AT1 (main player in bp regulation) and AT2 (mostly in fetus) receptors
-mediated by Ca
-AT1-->Gq-->PLC-->IP3-->Ca

Front 19

angII and vascular smooth muscle

Back 19

-arteriolar vasoconstriction --> inc bp
-hypertrophy via inc in migration, proliferation, hypertrophy, inc ECM

Front 20

angII and adrenal cortex

Back 20

-stimulates aldosterone biosynthesis and secretion
-promotes Na reabsorption indirectly

Front 21

central nervous system and angII

Back 21

-promotes thirst- dipsogenic
-promotes ADH release
-promotes positive water balance

Front 22

symp NS and angII

Back 22

-facilitates NE release and prevents its reuptake in symp neurons
-promotes epi secretion in adrenal medulla

Front 23

heart and angII

Back 23

-hypertrophy of cardiac myocytes
-increase in ECM production by fibroblasts
-inc catecholamines cause inc iontrophy

Front 24

mech of aldosterone

Back 24

-specific mineralocorticoid rec
-activates expression of target genes
-acts on kidney and heart

Front 25

where does angII work

Back 25

-adrenal cortex
-kidney
-CNS
-peripheral vasculature
-adrenal medulla
-periph symp NS
-heart

Front 26

aldosterone and kidney

Back 26

-acts on principal cells of the CD
-Na reabsorption and K secretion

Front 27

aldosterone and heart

Back 27

-cardiac fibrosis of both ventricles
-LV hypertrophy

Front 28

types of inhibitors of renin-angio system

Back 28

-ARBs (block AT1): losartan
-ACE inhibitors: captopril, enalapril, lisinopril
-B blockers: propanolol, metoprolol
-renin inhibitors: aliskrien
-aldosterone antags: spironolactone, eplerenone

Front 29

losartan

Back 29

-compet inhibit of angII at AT1
-treats HTN
-enhanced by diuretics
-c/i in pregnancy

Front 30

captopril

Back 30

-also, enalapril and lisinopril
-ACE inhibitors: inhibits angII formation and prevent degradation of bradykinin
-treat HTN and CHF (dec bp without affecting HR)

Front 31

captopril side effects

Back 31

-agranulocytosis
-rash
-proteinuria
-angioedema and cough (also enalapril and lisinopril)

Front 32

renin inhibitor

Back 32

-aliskiren
-non-peptide, specific for renin
-treats HTN with no change in HR
-enhanced by other anti-HTNs
-dec angII and aldosterone concentrations

Front 33

aldosterone inhibitor

Back 33

-spironolactone, eplerenone
-competitive inhib at mineralocorticoid rec
-diuretics
-reduce cardiac hypertrophy, heart failure