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65 Cards in this Set
- Front
- Back
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What is the rate limiting step in renin-angiotensin?
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release of renin
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What is the juxtaglomerular cell?
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modified SM cell in afferent arteriole.
contain renin granules |
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Where is the macula densa?
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specialized epithelial cells at the point where distal tubule & afferent arteriole
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What does the macula densa do?
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sense Na & regulate renin release
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What is the pattern of angiotesinogen to angiotensin III?
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angiotensinogen -renin-> angiotensin 1 (10) -ACE-> angiotensin 2 (8) -> 3 -angiotensinase A
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What is renin?
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protease that splits Leu-Leu of angiotensinogen to ang I
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Where is renin made?
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JG cells of kidneys
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What is renin inhibited by?
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aliskiren
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Where is angiotensinogen made?
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liver
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What end of angiotensinogen is active?
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amino (N) terminal
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What stimulates synthesis of angiotensinogen?
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estrogens & glucocorticoids
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Is angiotensin I active?
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no
10 aa |
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What is converting enzyme peptidyl dipeptidase?
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removes His-Leu from ang I to ang II making it active
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Where do you find ACE?
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vascular endothelium, lung, kidney, plasma
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What does ACE inactivate?
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bradykinin
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What inhibits ACE?
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captopril
Enalapril lisinopril |
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What is angiotensin 2?
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active 8 aa
t1/2 - 4 min |
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What is angiotensinase?
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non-specific amnio-peptidase & carboxypeptidase
inactivates Ang 1 & 2 |
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What is aldosterone?
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mineralocorticoid that acts on distal tubule & collecting duct to enhance Na reabsorption & K excretion
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What is aldosterone inhibited by?
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apironolactone & eplerenone
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Where is aldosterone synthesized?
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zona glomerulosa cells of adrenal cortex
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What stimulates the synthesis of aldosterone?
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potassium, ACTH & angiotensin II
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What are some sensors for renin release?
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intrarenal baroreceptors
macula densa SNS angiotensin 2 |
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What does the intrarenal baroreceptor sense?
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wall tension in the afferent arteriole
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How is wall tension related to renin?
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inversely
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What does the macula densa sense?
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sodium in the distal tubule
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How is sodium related to renin release?
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inversely
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How is the SNS mediated in kidneys?
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B1 adrenergic receptors on JG cells
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A reduction in sympathetic nerve activity does what to renin release?
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decreases it
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What are 2 beta blockers that reduce sympathetic nerve activity and therefore renin release?
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propranolol
metoprolol |
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How is angiotensin II directly fed back upon?
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inc aldo inc Na inc ECV inc BP therefore dec renin
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How is angiotesin II indirectly fed back upon?
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inc BP in baroreceptors dec renin release
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What does the AT1 receptor mediate?
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vasoconstriction
vascular proliferation aldosterone secretion cardiac myocyte proliferation increased sympathetic tone |
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What does the AT2 receptor mediate?
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vasodilation - NO
anti-proliferation apoptosis |
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What activates the AT1 & AT 2 receptors?
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angiotensin 2
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What is the mechanism of action of Angiotensin 2?
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mediated by calcium
Gq |
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What does Angiotensin 2 do to vascular SM?
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arteriolar vasoconstrictor
inc BP and TPR reflex bradycardia hypertrophy |
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What is the equation for BP?
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CO x TPR
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What effects CO?
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HR, contractility, preload, ECV
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What does angiotensin II do to the adrenal cortex?
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aldosterone synthesis
promotes Na resorption |
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What does angiotensin II do to the CNS?
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promotes ADH release
promotes postitive water balance |
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What does angiotensin II do to the sympathetic neuron?
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facilitates NE release
inhibits NE reuptake |
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What does angiotensin II do to the adrenal medulla?
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promotes epinepherine secretion
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What does angiotensin II do to the heart?
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hypertrophy
fibroblasts |
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What is the mechanism of action of aldosterone?
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mineralocorticoid
activates target genes |
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What inhibits aldosterone?
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spironolactone
eplerenone |
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What does aldosterone do to the kidney?
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acts on prinicpal cells of collecting duct to cause Na reabsorption & potassium secretion
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What does aldosterone do to the heart?
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cardiac fibrosis
LVH |
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What is the renin inhibitor?
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aliskiren
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What is the mechanism of action of aliskiren?
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potent active site
specific for renin |
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What is the half life of aliskiren?
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24 hours
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What is aliskiren used to treat?
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HTN
enhanced by diuretic, ACEi, angiotensin antagonist |
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What does aliskiren do to plasma concentrations of Angiotensin 2 & aldosterone?
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decreased
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What drugs block the AT1 receptors?
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losartan
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What is the effect of losartan?
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decreased proliferation, alldosterone, vasoconstriction, sympathetic tone which ulitmately decrease BP
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What is the pharmokinetics of losartan?
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slow onset of action
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Who is losartan contraindicated in?
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pregnancy
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What are the converting enzyme inhibitors?
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captopril, enalapril, lininopril
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What are ACE inhibitors used to treat?
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HTN & congestive cardiac failure
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What are the side effects of captopril?
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agranulocytosis, rash & proteinuria
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Who are ACE inhibitors contraindicated in?
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pregnant women
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What are the aldosterone antagonsits?
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spironolactone
eplerenone |
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What is the mechanism of action of aldosterone antagonists?
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competitive mineralocorticoidss
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What are spirolactone & eplerenone used to treat?
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reduce cardiac hypertrophy and heart failure
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What is the effect of aldosterone antagonsits on HR?
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none
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