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80 Cards in this Set
- Front
- Back
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How many drugs are there for the renin-angiotensin system and how do you remember them?
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9 - Captain enala listens to spiritual episcopalians promoting meetings with the almighty lord
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What are the ACE inhibitors?
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Captopril
Enalapril Lisinopril |
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What are the 2 mineralocorticoid receptor antagonists?
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Spironolactone
Eplerenone (spiritual episcopalians) |
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What are the 2 beta blockers used for the RAS?
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-Propanolol
-Metoprolol |
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What is the renin inhibitor?
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Aliskiren
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What is an antiotensin AT1 receptor antagonist?
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Losartan
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What happens to the RAS when there is a drop in blood pressure?
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It stimulates the JG cells of the afferent renal arteriole to release Renin
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What is Renin and what does it do?
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-Acid protease
-Cleaves Angiotensinogen into Angiotensin I by clipping between two Leu residues |
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What is Angiotensinogen also called? Where is it made? What stimulates its synthesis?
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alpha2-globulin, renin substrate
-Made in the liver -Synthesis is stimulated by Estrogen |
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What is Angiotensin I? How many amino acids does it have?
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An inactive peptide of 10 AAs
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What is Angiotensin I a substrate for?
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Angiotensin I converting enzyme (ACE)
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At what 4 sites is ACE located?
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-Lung
-Kidney -Plasma -Vascular endothelium |
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Where does ACE cleave Angiotensin I and what is the product/# of AAs?
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-Cleaves between Phe-His
-Product is Angiotensin II -Has 8 amino acids |
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What is the half life of angiotensin II?
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4 minutes
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What does Angiotensin II do during its 4 minutes of life?
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1. Global vasoconstriction
2. Aldosterone release from adrenal cortex (zona glomerulosa) |
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What is Angiotensin II a substrate for?
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Angiotensinase
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What is the product of Angiotensinase cleaving Ang II and how many AA's does it have?
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Angiotensin III
Has 7 amino acids |
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What can Ang III do?
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Also stimulates aldosterone release
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What action does Aldosterone have? What are its 2 physiological effect?
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Stimulates sodium reabsorption and K excretion
-Increased ECF volume -Increased blood pressure |
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What is Aldosterone synthesis stimulated by? (3 things)
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-Potassium
-ACTH -Angiotensin II |
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What effect does renin have on the kidney?
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Negative feedback; suppresses renin release.
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What are the 3 constituents of the Juxtaglomerular apparatus?
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-Juxtaglomerular cells
-Macula densa cells -Renal Sympathetic nerves |
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What kind of cells are the JG cells and where are they located?
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-Modified smooth muscle cells
-Located in tunica media of the afferent arteriole |
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What do the JG cells contain and what stimulates their release?
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-Contain renin-filled secretory granules
-Stimulated by renal SNS nerves |
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What kind of cells are the macula densa cells and where are they located?
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-Specialized epithelial cells
-Found at the point where the distal tubule comes in close contact with afferent arteriole |
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What 2 functions do the macula densa cells accomplish?
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1. Sense decreases in tubular sodium
2. Regulate Renin release |
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Where are the renal sympathetic nerves located?
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In the tunica media of the afferent arteriole (where the JG cells are)
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So the 2 things that regulate renin release from the JG cells of the afferent arteriole are:
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-Renal sympathetic nerves
-Macula densa cells in the distal tubule |
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What is the rate limiting step in activating the RAS?
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Renin release
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What are 4 mechanisms of controlling renin release from JG cells?
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1. Intrarenal baroreceptor
2. Macula densa 3. Renal sympathetic nerves 4. Angiotensin II |
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How does the Intrarenal baroreceptor control Renin release?
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By sensing wall tension (perfusion pressure) of the afferent artiole which is inversely related to Renin release
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What is the law that governs renin release?
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Renal Perfusion Pressure = RPP
RPP = 1/renin release |
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So what is renin secretion inversely related to?
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Renal perfusion pressure
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What are 2 conditions in which RPP is elevated? What will renin release do?
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-Increased vascular pressure
-Renal aff arteriole constriction Decreases renin release |
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What are 2 conditions in which RPP is decreased? What will renin release do?
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-Decreased vascular pressure
-Renal aff arteriole dilation Increases Renin release |
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What is an physiologic example of decreased renal bloodflow?
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Renal artery stenosis
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What effect does the decreased RBF in renal artery stenosis have on the RAS?
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-Decreased blood pressure distal to the stenotic vessel
-Intrarenal baroreceptor senses decreased wall tension/RPP -Renin release increases |
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What effect does the increased renin release in renal artery stenosis have on circulation?
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-Increases blood pressure
-Result is systemic hypertension |
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Where the intrarenal baroreceptor detects RPP and wall tension, the Macula densa cells in the distal tubule sense:
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Changes in sodium load (UnaV)in the distal tubule
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What is the relationship between urine sodium load and renin release?
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Inverse; UnaV = 1/renin release
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What are 2 things that cause there to be increased UnaV?
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-Mineralocorticoids (Aldo)
-Increased dietary salt |
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What effect will Aldosterone and a high salt diet have on Renin release?
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Decrease it
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What are 4 conditions in which UnaV will be decreased? How will they effect Renin release?
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-Decreased salt intake
-Sodium deprivation -Diuretic treatment -Decreased GFR Response is increased Renin |
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Where are the renal sympathetic nerves located?
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In the tunica media of the afferent arteriole
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Where are the receptors for NE released by the renal SNS nerves? What type of receptors are they?
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B1 adrenergics located right on the JG cells!
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What is the effect of NE release by the renal sympathetic nerves?
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Increased renin release
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What else can stimulate the B1 adrenergic receptors on the JG cells?
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Beta agonists like isoproterenol
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What 2 drugs block the activation of B1 receptors on the renal JG cells?
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-Propanolol
-Metoprolol |
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How does Angiotensin II regulate renin release?
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By shortloop feedback, acting to directly inhibit the JG cells from releasing renin.
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What mediates Ang II regulation of JG cells releasing renin?
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AT1 receptors on the JG cells
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What effect will AT1 receptor antagonists or ACE inhibition have on Renin release?
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It will increase because there will be no AngII neg feedback inhibition of renin release
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What drug blocks AT1 receptors?
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Losartan
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What are 2 types of receptors for Angiotensin II?
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AT1 receptors
AT2 receptors |
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What 2 effects are seen when Ang II binds AT1 receptors?
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-Global vasoconstriction
-Aldosterone release |
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What 2 effects are seen when AngII binds AT2 receptors?
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-Vasodilation
-Apoptosis |
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What are the dominant receptors?
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AT1
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What type of receptor is the AT1 receptor, and what is the mechanism that occurs when AngII binds to it?
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-GPCR
-Binding stimulates Gq which activates PLC and cleaves PIP2 into IP3/DAG and increases Ca |
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So the effects of Ang II at the AT1 receptor are mediated by:
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Calcium
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And the 2 major results of AT1 activation by Ang II are:
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-Global vasoconstriction
-Aldosterone release |
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At what 4 sites are Ang II receptors located?
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-Vascular smooth muscle
-Adrenal cortex -CNS -Symp NS |
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What type of vessels mainly have AT1 receptors and what 3 effects does Ang II have on circulation?
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-Arterioles
-Ang II causes vasoconstriction -Increased BP, Renal Perf Prsr, decreased renin release |
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What is the effect of increased blood pressure on heartrate?
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Reflex bradycardia
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What effect does Ang II have on vessel wall calibur?
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Hypertrophy - increases the wall:lumen ratio
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What effect does Ang II have when it binds its AT1 receptors on the adrenal cortex?
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Increased Aldosterone biosynthesis and secretion
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What effect does Aldosterone have on:
-Sodium -Blood pressure -Renin release |
-Increases Na reabsorption
-Increases blood pressure -Inhibits renin release |
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What 2 things does Ang II affect in the CNS? What is the physiological result?
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-Stimulates thirst
-Stimulates ADH release -Increases water reabsorption |
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What 2 SNS components can be modified by Ang II?
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-Sympathetic neurons
-Adrenal medulla |
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How does Ang II affect sympathetic neurons? (2 ways)
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1. Facilitates NE release
2. Inhibits NE reuptake So there's more NE in the synapse |
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How does Ang II inhibit NE reuptake?
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By inhibiting NET - so its like Cocaine and TCAs
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How does Ang II affect the adrenal medulla?
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Promotes epinephrine secretion
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In addition to its effects on vascular sm musc, the adrenal cortex, CNS and SNS, what other organ is affected by Ang II?
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The heart
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What effects does Ang II have on the heart?
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-Hypertrophy of cardiac myocytes
-Increased production of ECM by fibroblasts |
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What are the effects of Aldosterone mediated by?
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A specific mineralocorticoid receptor
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What does Aldo binding its receptor stimulate?
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Expression of target genes
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What are the effects of Aldosterone inhibited by?
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Spironolactone/Eplerenone
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What are Spironolactone and Eplerenone?
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Mineralocorticoid receptor antagonists
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What are the 2 target tissues of aldosterone?
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-Heart
-Kidney |
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What cells are acted on by aldosterone in the kidney?
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Principal cells of the collecting duct
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What is the effect seen when Aldo stimulates its receptors on the principal cells?
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-Increased sodium reabsorption
-Increased Potassium secretion |
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What effect does Aldosterone have on the heart?
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-Fibrosis of both ventricles
-Left ventricular hypertrophy |
