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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?
Maintains blood pressure
Salt and water balance
What are two other roles the renin-angiotensin system plays in?
Vasoconstriction of vessels
Inflammation
The RAS is composed of?
systemic (vascular) and local tissue system
T/F The RAS is involved in short term regulation of blood pressure only.
False- involved in short and long term regulation of blood pressure
Is the rate limiting factor in the activity of the systemic renin angiotensin system
Angiotensinogen
Angiotensinogen is primarily synthesized in the _____
hepatocytes found in the liver
In adipose tissue angiotensinogen mRNA is upregulated by what?
Insulin
In the hepatocytes angiotensinogen mRNA is upregulated by what?
Estrogen
Angiotensinogen is cleaved by the what enzyme?
Renin
Angiotensinogen is cleaved into what?
Angiotensin I
Synthesis of angiotensinogen can be stimulated by what?
Inflammation
Angiotensin II
Angiotensin II may exert what sort of feedback regulation via what sort of receptor.
Positive Feedback
AT1 receptor
Several lines of investigation suggest that angiotensinogen contributes to what phenotype?
Hypertensive
Angiotensinogen is the protein from which angiotensins are formed by what type of reactions?
Proteolytic Cleavage reactions
Is a highly substrate-and species-specific aspartyl protease enzyme
Renin
How many amino acids are lost in the reaction involving renin that created angiotensin I from angiotensinogen
four
14aa Angiotensinogen to a 10aa Ang I
What cells are the systemic source for renin synthesis, storage and release?
Juxtaglomerular (JG) cells
What is the initial step in the synthesis of renin?
The formation of the pre-pro-renin by renin mRNA
How many amino acids make up the "pre" portion of pre-pro-renin?
23 aa
How many amino acids make up the "pro" portion of pre-pro-renin?
43 aa
Where in the cell is the "pro" portion of pre-pro-renin cleaved to renin?
in the golgi apparatus
The active renin molecule has how much energy?
40,000 Daltons
What enzyme mediates the cleavage and activation of renin?
Cathepsin B
Renin is excreted from the cell into the blood stream by what action?
exocytosis
What are the three regulatory pathways of the JG cells that control the secretion of renin?
1. Macula densa pathway
2. Intrarenal baroreceptor pathway
3. Beta-adrenergic receptor pathway
How does the regulatory macula densa pathway work?
They monitor sodium levels.
Low sodium level is the signal that initiates a series of steps that ultimately stimulates renin release
How does renin effect sodium levels?
Renin helps to create angiotensin which interacts with aldosteron which causes sodium uptake in the body
The macula densa pathway is like more of what type of system for regulating renin release?
chronic adaptive system
What are two other molecules activated by the macula densa pathway that stimulate the release of renin?
PGE2 and Cox 2 enzyme
Dietary sodium restriction results in an upregulation of what?
The inducible Cox 2 expression
What substance inhibits renin release?
Adenosine
Where are the renal baroreceptors located?
in the afferent arterioles
How do baroreceptors effect renin secretion?
They stimulate renin secretion in response to reduced renal perfusion pressure and attenuates renin secretion as renal perfusion is elevated.
What pathway is the most powerful regulator of renin release?
The Baroreceptor Pathway
The JG cells are directly innervated by what nerves?
Sympathetic nerves
Direct stimulation of the sympathetic nerves innervating the JG cells causes what?
An increase in renin release
The Beta-adrenergic receptor pathway is what type of pathway?
Acute pathway
Which pathway provides rapid activation of the RAS which is provoked by such stimuli as stress and posture?
Beta-adrenergic Receptor Pathway
What sort of physiological network are the three renin regulatory systems in?
Short-loop negative feedback system

Long-Loop negative feedback
Increase in renin secretion will result in what?
an increase in Ang II
Ang II stimulates what on the JG cells?
AT1R
Stimulated AT1R on the JG cells does what?
inhibits renin release
Ang II increases what via AT1R?
Blood Pressure
How does an increase in blood pressure inhibit renin release?
Throught the Baroreceptor pathway
cAMP it he primary second messenger for what in the renin regulatory loops?
Beta-adrenergic and PGE
An increase in cAMP causes what in the renin regulatory loops?
Increase in Renin
Renin release is inhibited by an increase in what intracellular ion?
Ca ++
In the renin regulatory loop cGMP acts as what?
An inhibitory second messenger
How would factors that stimulate cGMP affect renin release?
Inhibit renin release
Loop Diuretics do what in the renin pathways?
Block NaCl reabsorption which then stimulates the macula densa pathway to secrete more renin
How do NSAIDS affect renin release?
They inhibit PG which decreased renin release
How do ACE inhibitors and AT1R blockers affect renin release?
They interrupt the feedback systems which then causes an increase in renin release
How do Beta-adrenergic blockers and central acting sympatholytic drugs affect renin release?
They inhibit the adrenergic pathway and therefore decrease renin release
The macula densa chemoreceptors act as what type of regulator in the renin release system?
Long term regulator
The Juxaglomerular baroreceptors act as what type of regulator in the renin release system?
Most powerful regulator
The Sympathetic stimulation act as what type of regulator in the renin release system?
Most rapid regulator
An ubiquitous enzyme, found in the plasma and is a membrane-bound extoenzyme predominately on endothelial and epithelial cells.
Angiotensin Converting Enzyme (ACE)
What is the major physiological function of ACE?
Convert Ang 1 to Ang II
ACE inactivates what regulator of blood pressure?
Bradykinins (which act as vasodialtors reducing pressure while Angs increase pressure)
What enzyme acts as the angiotenisn converter?
Chymase
Endothelial ACE contains how many inhibitory binding sites per molecule?
Two
Homozygous individuals for the insertion polymorphism ACE gene have what?
Lower levels of ACE in the plasma
Homozygous individuals with the deletion polymorphism (DD) have what?
Double the circulating levels of ACE
ACE is found on endothelial cells especially where in the body?
lungs
retina
brain
Ace is found on epithelial cells especially where in the body?
kidney and gut
ACE2 is expressed in the endothelial cells located where in the body?
heart
testis
kidney
ACE2 catalyzes the formation of what vasodilator molecule from both Ang I and Ang II?
Ang I-7
ACE2 may act as what of Ang II action?
An antagonist
How is ACE 2 affected by ACE inhibitors?
It is insensitive to ACE inhibitors
ACE 2 levels increase in what two disease states?
Hypertension
Heart Failure
What are the two specific receptors of Ang II?
AT1 and AT2
AT1 and AT2 are what type of proteins?
Members of G protein coupled receptor family with 7 transmembrane regions
What mediates most of the biological effects of AngII?
AT1R
Glucocorticoids and Insulin do what to the number of AT1R receptors?
Increase the number of receptors
Miineralocorticoids and Estrogens do what to the number of AT1R receptors?
Decrease the number of receptors
What receptor is widely distributed in the fetal tissues?
AT2R
How does AT2R interact with AngII on AT1 receptors?
In opposition to
What receptor is re-expressed in times of injury?
AT2R
Inhibition of ACE initially causes what?
Increase in Ang I concentration
Decrease in Ang II concentration
Decrease in Aldosterone concentration
Why could plasma levels of Ang II not remain suppressed during chronic therapy of ACEI?
Incomplete block of the enzyme

Increase in Ang I may exceed inhibitory capacity of ACEI

Another rout for Ang II formation through Chymase
ACE inhibition blocks the degradation of what which inhibits what which can cause what?
Ang I-7
Ang II action
Allows for vasodilation and antiproliferation
ACE inhibition increase what which also can what?
Bradykinin
Vasodilate
ACE inhibition increase what levels?
ACE 2 and Ang I-7
Local RAS systems are considered part of what system?
Paracrine/autocrine system
Locally formed angiotensins can act as what?
growth factors
neurotransmitters
smooth muscle constrictors
Weight loss decreases what in the angiotensin cycle?
ACE
What are the two major roles of Ang II?
Regulation of blood pressure
Sodium homeostasis
Ang II directly causes what primarily in the precapillary arterioles?
Vasoconstriction
How does Ang II enhance peripheral noradrenergic neutoransmission?
It augments NE release
Inhibits uptake of NE
Enhances vascular response to NE
What are Ang II effects on the central nervous system?
increases sympathetic outflow

Increases arterial pressure through baroreceptor mediated sympathetic discharge

Causes dipogenic effect (water uptake)

Enhances the release of ADH
What hormones does Ang II stimulate to be released and form where?
Catecholamines from the medulla
Aldosterone form the cortex
Ang II stimulates what in vascular smooth muscle (VSM)
Hypertrophy
Vasoconstriction
Mitogenesis
RAS plays a role in what disease state?
Atherosclerosis
RAS is required for the development of what?
normal renal function
RAS generates what?
Reactive oxygen species
RAS leads to what in the endothelial?
endothelial dysfunction
Ang II stimulates what in a pro-thrombotic effect?
PAI-1 (plasminogen activator inhibitor)
Angiotensin plays an important role in what process?
Hemorrhaging
Name the pro-inflammatory effects Ang II has.
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
Where in the adrenal cortex is aldosterone produced?
zona glomerulosa
Secretion of aldosterone is regulated primarily by what?
Ang II and potassium
Aldosterone acts on renal and other epithelia to do what?
Enhance sodium reabsorption and increase the excretion of potassium and hydrogen ions