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102 Cards in this Set
- Front
- Back
What are the two major effects of the renin-angiotensin system in the body?
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Maintains blood pressure
Salt and water balance |
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What are two other roles the renin-angiotensin system plays in?
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Vasoconstriction of vessels
Inflammation |
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The RAS is composed of?
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systemic (vascular) and local tissue system
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T/F The RAS is involved in short term regulation of blood pressure only.
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False- involved in short and long term regulation of blood pressure
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Is the rate limiting factor in the activity of the systemic renin angiotensin system
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Angiotensinogen
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Angiotensinogen is primarily synthesized in the _____
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hepatocytes found in the liver
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In adipose tissue angiotensinogen mRNA is upregulated by what?
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Insulin
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In the hepatocytes angiotensinogen mRNA is upregulated by what?
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Estrogen
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Angiotensinogen is cleaved by the what enzyme?
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Renin
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Angiotensinogen is cleaved into what?
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Angiotensin I
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Synthesis of angiotensinogen can be stimulated by what?
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Inflammation
Angiotensin II |
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Angiotensin II may exert what sort of feedback regulation via what sort of receptor.
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Positive Feedback
AT1 receptor |
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Several lines of investigation suggest that angiotensinogen contributes to what phenotype?
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Hypertensive
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Angiotensinogen is the protein from which angiotensins are formed by what type of reactions?
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Proteolytic Cleavage reactions
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Is a highly substrate-and species-specific aspartyl protease enzyme
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Renin
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How many amino acids are lost in the reaction involving renin that created angiotensin I from angiotensinogen
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four
14aa Angiotensinogen to a 10aa Ang I |
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What cells are the systemic source for renin synthesis, storage and release?
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Juxtaglomerular (JG) cells
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What is the initial step in the synthesis of renin?
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The formation of the pre-pro-renin by renin mRNA
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How many amino acids make up the "pre" portion of pre-pro-renin?
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23 aa
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How many amino acids make up the "pro" portion of pre-pro-renin?
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43 aa
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Where in the cell is the "pro" portion of pre-pro-renin cleaved to renin?
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in the golgi apparatus
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The active renin molecule has how much energy?
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40,000 Daltons
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What enzyme mediates the cleavage and activation of renin?
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Cathepsin B
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Renin is excreted from the cell into the blood stream by what action?
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exocytosis
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What are the three regulatory pathways of the JG cells that control the secretion of renin?
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1. Macula densa pathway
2. Intrarenal baroreceptor pathway 3. Beta-adrenergic receptor pathway |
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How does the regulatory macula densa pathway work?
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They monitor sodium levels.
Low sodium level is the signal that initiates a series of steps that ultimately stimulates renin release |
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How does renin effect sodium levels?
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Renin helps to create angiotensin which interacts with aldosteron which causes sodium uptake in the body
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The macula densa pathway is like more of what type of system for regulating renin release?
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chronic adaptive system
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What are two other molecules activated by the macula densa pathway that stimulate the release of renin?
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PGE2 and Cox 2 enzyme
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Dietary sodium restriction results in an upregulation of what?
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The inducible Cox 2 expression
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What substance inhibits renin release?
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Adenosine
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Where are the renal baroreceptors located?
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in the afferent arterioles
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How do baroreceptors effect renin secretion?
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They stimulate renin secretion in response to reduced renal perfusion pressure and attenuates renin secretion as renal perfusion is elevated.
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What pathway is the most powerful regulator of renin release?
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The Baroreceptor Pathway
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The JG cells are directly innervated by what nerves?
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Sympathetic nerves
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Direct stimulation of the sympathetic nerves innervating the JG cells causes what?
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An increase in renin release
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The Beta-adrenergic receptor pathway is what type of pathway?
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Acute pathway
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Which pathway provides rapid activation of the RAS which is provoked by such stimuli as stress and posture?
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Beta-adrenergic Receptor Pathway
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What sort of physiological network are the three renin regulatory systems in?
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Short-loop negative feedback system
Long-Loop negative feedback |
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Increase in renin secretion will result in what?
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an increase in Ang II
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Ang II stimulates what on the JG cells?
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AT1R
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Stimulated AT1R on the JG cells does what?
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inhibits renin release
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Ang II increases what via AT1R?
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Blood Pressure
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How does an increase in blood pressure inhibit renin release?
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Throught the Baroreceptor pathway
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cAMP it he primary second messenger for what in the renin regulatory loops?
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Beta-adrenergic and PGE
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An increase in cAMP causes what in the renin regulatory loops?
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Increase in Renin
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Renin release is inhibited by an increase in what intracellular ion?
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Ca ++
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In the renin regulatory loop cGMP acts as what?
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An inhibitory second messenger
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How would factors that stimulate cGMP affect renin release?
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Inhibit renin release
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Loop Diuretics do what in the renin pathways?
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Block NaCl reabsorption which then stimulates the macula densa pathway to secrete more renin
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How do NSAIDS affect renin release?
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They inhibit PG which decreased renin release
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How do ACE inhibitors and AT1R blockers affect renin release?
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They interrupt the feedback systems which then causes an increase in renin release
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How do Beta-adrenergic blockers and central acting sympatholytic drugs affect renin release?
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They inhibit the adrenergic pathway and therefore decrease renin release
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The macula densa chemoreceptors act as what type of regulator in the renin release system?
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Long term regulator
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The Juxaglomerular baroreceptors act as what type of regulator in the renin release system?
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Most powerful regulator
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The Sympathetic stimulation act as what type of regulator in the renin release system?
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Most rapid regulator
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An ubiquitous enzyme, found in the plasma and is a membrane-bound extoenzyme predominately on endothelial and epithelial cells.
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Angiotensin Converting Enzyme (ACE)
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What is the major physiological function of ACE?
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Convert Ang 1 to Ang II
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ACE inactivates what regulator of blood pressure?
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Bradykinins (which act as vasodialtors reducing pressure while Angs increase pressure)
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What enzyme acts as the angiotenisn converter?
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Chymase
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Endothelial ACE contains how many inhibitory binding sites per molecule?
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Two
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Homozygous individuals for the insertion polymorphism ACE gene have what?
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Lower levels of ACE in the plasma
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Homozygous individuals with the deletion polymorphism (DD) have what?
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Double the circulating levels of ACE
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ACE is found on endothelial cells especially where in the body?
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lungs
retina brain |
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Ace is found on epithelial cells especially where in the body?
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kidney and gut
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ACE2 is expressed in the endothelial cells located where in the body?
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heart
testis kidney |
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ACE2 catalyzes the formation of what vasodilator molecule from both Ang I and Ang II?
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Ang I-7
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ACE2 may act as what of Ang II action?
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An antagonist
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How is ACE 2 affected by ACE inhibitors?
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It is insensitive to ACE inhibitors
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ACE 2 levels increase in what two disease states?
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Hypertension
Heart Failure |
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What are the two specific receptors of Ang II?
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AT1 and AT2
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AT1 and AT2 are what type of proteins?
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Members of G protein coupled receptor family with 7 transmembrane regions
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What mediates most of the biological effects of AngII?
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AT1R
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Glucocorticoids and Insulin do what to the number of AT1R receptors?
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Increase the number of receptors
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Miineralocorticoids and Estrogens do what to the number of AT1R receptors?
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Decrease the number of receptors
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What receptor is widely distributed in the fetal tissues?
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AT2R
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How does AT2R interact with AngII on AT1 receptors?
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In opposition to
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What receptor is re-expressed in times of injury?
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AT2R
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Inhibition of ACE initially causes what?
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Increase in Ang I concentration
Decrease in Ang II concentration Decrease in Aldosterone concentration |
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Why could plasma levels of Ang II not remain suppressed during chronic therapy of ACEI?
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Incomplete block of the enzyme
Increase in Ang I may exceed inhibitory capacity of ACEI Another rout for Ang II formation through Chymase |
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ACE inhibition blocks the degradation of what which inhibits what which can cause what?
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Ang I-7
Ang II action Allows for vasodilation and antiproliferation |
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ACE inhibition increase what which also can what?
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Bradykinin
Vasodilate |
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ACE inhibition increase what levels?
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ACE 2 and Ang I-7
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Local RAS systems are considered part of what system?
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Paracrine/autocrine system
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Locally formed angiotensins can act as what?
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growth factors
neurotransmitters smooth muscle constrictors |
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Weight loss decreases what in the angiotensin cycle?
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ACE
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What are the two major roles of Ang II?
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Regulation of blood pressure
Sodium homeostasis |
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Ang II directly causes what primarily in the precapillary arterioles?
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Vasoconstriction
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How does Ang II enhance peripheral noradrenergic neutoransmission?
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It augments NE release
Inhibits uptake of NE Enhances vascular response to NE |
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What are Ang II effects on the central nervous system?
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increases sympathetic outflow
Increases arterial pressure through baroreceptor mediated sympathetic discharge Causes dipogenic effect (water uptake) Enhances the release of ADH |
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What hormones does Ang II stimulate to be released and form where?
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Catecholamines from the medulla
Aldosterone form the cortex |
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Ang II stimulates what in vascular smooth muscle (VSM)
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Hypertrophy
Vasoconstriction Mitogenesis |
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RAS plays a role in what disease state?
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Atherosclerosis
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RAS is required for the development of what?
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normal renal function
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RAS generates what?
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Reactive oxygen species
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RAS leads to what in the endothelial?
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endothelial dysfunction
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Ang II stimulates what in a pro-thrombotic effect?
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PAI-1 (plasminogen activator inhibitor)
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Angiotensin plays an important role in what process?
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Hemorrhaging
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Name the pro-inflammatory effects Ang II has.
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Act as a Cytokine (growth promoter and pro-inflammatory modulator)
Increase vascular permeability Participates in the recruitment of cells Regulates the expression of adhesion molecules and chemokines Participate in tissue repair |
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Where in the adrenal cortex is aldosterone produced?
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zona glomerulosa
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Secretion of aldosterone is regulated primarily by what?
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Ang II and potassium
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Aldosterone acts on renal and other epithelia to do what?
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Enhance sodium reabsorption and increase the excretion of potassium and hydrogen ions
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