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80 Cards in this Set

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How many drugs are there for the renin-angiotensin system and how do you remember them?
9 - Captain enala listens to spiritual episcopalians promoting meetings with the almighty lord
What are the ACE inhibitors?
Captopril
Enalapril
Lisinopril
What are the 2 mineralocorticoid receptor antagonists?
Spironolactone
Eplerenone
(spiritual episcopalians)
What are the 2 beta blockers used for the RAS?
-Propanolol
-Metoprolol
What is the renin inhibitor?
Aliskiren
What is an antiotensin AT1 receptor antagonist?
Losartan
What happens to the RAS when there is a drop in blood pressure?
It stimulates the JG cells of the afferent renal arteriole to release Renin
What is Renin and what does it do?
-Acid protease
-Cleaves Angiotensinogen into Angiotensin I by clipping between two Leu residues
What is Angiotensinogen also called? Where is it made? What stimulates its synthesis?
alpha2-globulin, renin substrate
-Made in the liver
-Synthesis is stimulated by Estrogen
What is Angiotensin I? How many amino acids does it have?
An inactive peptide of 10 AAs
What is Angiotensin I a substrate for?
Angiotensin I converting enzyme (ACE)
At what 4 sites is ACE located?
-Lung
-Kidney
-Plasma
-Vascular endothelium
Where does ACE cleave Angiotensin I and what is the product/# of AAs?
-Cleaves between Phe-His
-Product is Angiotensin II
-Has 8 amino acids
What is the half life of angiotensin II?
4 minutes
What does Angiotensin II do during its 4 minutes of life?
1. Global vasoconstriction
2. Aldosterone release from adrenal cortex (zona glomerulosa)
What is Angiotensin II a substrate for?
Angiotensinase
What is the product of Angiotensinase cleaving Ang II and how many AA's does it have?
Angiotensin III
Has 7 amino acids
What can Ang III do?
Also stimulates aldosterone release
What action does Aldosterone have? What are its 2 physiological effect?
Stimulates sodium reabsorption and K excretion
-Increased ECF volume
-Increased blood pressure
What is Aldosterone synthesis stimulated by? (3 things)
-Potassium
-ACTH
-Angiotensin II
What effect does renin have on the kidney?
Negative feedback; suppresses renin release.
What are the 3 constituents of the Juxtaglomerular apparatus?
-Juxtaglomerular cells
-Macula densa cells
-Renal Sympathetic nerves
What kind of cells are the JG cells and where are they located?
-Modified smooth muscle cells
-Located in tunica media of the afferent arteriole
What do the JG cells contain and what stimulates their release?
-Contain renin-filled secretory granules
-Stimulated by renal SNS nerves
What kind of cells are the macula densa cells and where are they located?
-Specialized epithelial cells
-Found at the point where the distal tubule comes in close contact with afferent arteriole
What 2 functions do the macula densa cells accomplish?
1. Sense decreases in tubular sodium
2. Regulate Renin release
Where are the renal sympathetic nerves located?
In the tunica media of the afferent arteriole (where the JG cells are)
So the 2 things that regulate renin release from the JG cells of the afferent arteriole are:
-Renal sympathetic nerves
-Macula densa cells in the distal tubule
What is the rate limiting step in activating the RAS?
Renin release
What are 4 mechanisms of controlling renin release from JG cells?
1. Intrarenal baroreceptor
2. Macula densa
3. Renal sympathetic nerves
4. Angiotensin II
How does the Intrarenal baroreceptor control Renin release?
By sensing wall tension (perfusion pressure) of the afferent artiole which is inversely related to Renin release
What is the law that governs renin release?
Renal Perfusion Pressure = RPP

RPP = 1/renin release
So what is renin secretion inversely related to?
Renal perfusion pressure
What are 2 conditions in which RPP is elevated? What will renin release do?
-Increased vascular pressure
-Renal aff arteriole constriction
Decreases renin release
What are 2 conditions in which RPP is decreased? What will renin release do?
-Decreased vascular pressure
-Renal aff arteriole dilation
Increases Renin release
What is an physiologic example of decreased renal bloodflow?
Renal artery stenosis
What effect does the decreased RBF in renal artery stenosis have on the RAS?
-Decreased blood pressure distal to the stenotic vessel
-Intrarenal baroreceptor senses decreased wall tension/RPP
-Renin release increases
What effect does the increased renin release in renal artery stenosis have on circulation?
-Increases blood pressure
-Result is systemic hypertension
Where the intrarenal baroreceptor detects RPP and wall tension, the Macula densa cells in the distal tubule sense:
Changes in sodium load (UnaV)in the distal tubule
What is the relationship between urine sodium load and renin release?
Inverse; UnaV = 1/renin release
What are 2 things that cause there to be increased UnaV?
-Mineralocorticoids (Aldo)
-Increased dietary salt
What effect will Aldosterone and a high salt diet have on Renin release?
Decrease it
What are 4 conditions in which UnaV will be decreased? How will they effect Renin release?
-Decreased salt intake
-Sodium deprivation
-Diuretic treatment
-Decreased GFR
Response is increased Renin
Where are the renal sympathetic nerves located?
In the tunica media of the afferent arteriole
Where are the receptors for NE released by the renal SNS nerves? What type of receptors are they?
B1 adrenergics located right on the JG cells!
What is the effect of NE release by the renal sympathetic nerves?
Increased renin release
What else can stimulate the B1 adrenergic receptors on the JG cells?
Beta agonists like isoproterenol
What 2 drugs block the activation of B1 receptors on the renal JG cells?
-Propanolol
-Metoprolol
How does Angiotensin II regulate renin release?
By shortloop feedback, acting to directly inhibit the JG cells from releasing renin.
What mediates Ang II regulation of JG cells releasing renin?
AT1 receptors on the JG cells
What effect will AT1 receptor antagonists or ACE inhibition have on Renin release?
It will increase because there will be no AngII neg feedback inhibition of renin release
What drug blocks AT1 receptors?
Losartan
What are 2 types of receptors for Angiotensin II?
AT1 receptors
AT2 receptors
What 2 effects are seen when Ang II binds AT1 receptors?
-Global vasoconstriction
-Aldosterone release
What 2 effects are seen when AngII binds AT2 receptors?
-Vasodilation
-Apoptosis
What are the dominant receptors?
AT1
What type of receptor is the AT1 receptor, and what is the mechanism that occurs when AngII binds to it?
-GPCR
-Binding stimulates Gq which activates PLC and cleaves PIP2 into IP3/DAG and increases Ca
So the effects of Ang II at the AT1 receptor are mediated by:
Calcium
And the 2 major results of AT1 activation by Ang II are:
-Global vasoconstriction
-Aldosterone release
At what 4 sites are Ang II receptors located?
-Vascular smooth muscle
-Adrenal cortex
-CNS
-Symp NS
What type of vessels mainly have AT1 receptors and what 3 effects does Ang II have on circulation?
-Arterioles
-Ang II causes vasoconstriction
-Increased BP, Renal Perf Prsr, decreased renin release
What is the effect of increased blood pressure on heartrate?
Reflex bradycardia
What effect does Ang II have on vessel wall calibur?
Hypertrophy - increases the wall:lumen ratio
What effect does Ang II have when it binds its AT1 receptors on the adrenal cortex?
Increased Aldosterone biosynthesis and secretion
What effect does Aldosterone have on:
-Sodium
-Blood pressure
-Renin release
-Increases Na reabsorption
-Increases blood pressure
-Inhibits renin release
What 2 things does Ang II affect in the CNS? What is the physiological result?
-Stimulates thirst
-Stimulates ADH release
-Increases water reabsorption
What 2 SNS components can be modified by Ang II?
-Sympathetic neurons
-Adrenal medulla
How does Ang II affect sympathetic neurons? (2 ways)
1. Facilitates NE release
2. Inhibits NE reuptake
So there's more NE in the synapse
How does Ang II inhibit NE reuptake?
By inhibiting NET - so its like Cocaine and TCAs
How does Ang II affect the adrenal medulla?
Promotes epinephrine secretion
In addition to its effects on vascular sm musc, the adrenal cortex, CNS and SNS, what other organ is affected by Ang II?
The heart
What effects does Ang II have on the heart?
-Hypertrophy of cardiac myocytes
-Increased production of ECM by fibroblasts
What are the effects of Aldosterone mediated by?
A specific mineralocorticoid receptor
What does Aldo binding its receptor stimulate?
Expression of target genes
What are the effects of Aldosterone inhibited by?
Spironolactone/Eplerenone
What are Spironolactone and Eplerenone?
Mineralocorticoid receptor antagonists
What are the 2 target tissues of aldosterone?
-Heart
-Kidney
What cells are acted on by aldosterone in the kidney?
Principal cells of the collecting duct
What is the effect seen when Aldo stimulates its receptors on the principal cells?
-Increased sodium reabsorption
-Increased Potassium secretion
What effect does Aldosterone have on the heart?
-Fibrosis of both ventricles
-Left ventricular hypertrophy