Term
| The RAAS major effect is to |
|
Definition
| maintain blood pressure and salt/water balance |
|
|
Term
| The RAAS is composed of a ___________ (vascular) and a _____________ (tissue) system. |
|
Definition
|
|
Term
| T/F: The RAAS is only involved with short term regulation of BP. |
|
Definition
| False; short and long term regulation |
|
|
Term
| What is the RLS of the systemic RAAS? |
|
Definition
|
|
Term
| Angiotensinogen is made in many cells/tissues. It primarily comes from ____________ and can be found in other places such as the CNS, heart, kidney, fat cells, etc. |
|
Definition
|
|
Term
| In the hepatocytes ________________________ is processed and constitutively secreted...is not stored. (Continually made and released) |
|
Definition
|
|
Term
| Adipose tissue angiotensinogen mRNA is upregulated by ____________. Whereas hepatocyte angiotensinogen mRNA is upregulated by ___________. |
|
Definition
|
|
Term
| Angiotensinogen + _____________ = (__________peptide) Ang I |
|
Definition
|
|
Term
| T/F: The control of angiotensinogen release is under transcriptional control. |
|
Definition
True
Glucocorticoids, insulin, estrogen, TH, and selected cytokines |
|
|
Term
| Synthesis of angiotensinogen is stimulated by _____________ and ____________. |
|
Definition
|
|
Term
| Since Ang II can stimulate the synthesis of angiotensinogen then it exerts a _____________ regulation via an ____________ receptor. |
|
Definition
|
|
Term
| There is an association of angiotensinogen levels with the _____________ phenotype. |
|
Definition
|
|
Term
| Renin is a highly substrate-and-species specific ________ protease _________. |
|
Definition
|
|
Term
| Angiotensinogen is a _______ peptide and _________ forms it into a 10 A.A peptide. |
|
Definition
|
|
Term
| Where is the systemic source of Renin made, stored and released? |
|
Definition
| Juxtaglomerular cells (JG) |
|
|
Term
| What is the initial step in renin synthesis? |
|
Definition
| The formation of pre-pro-renin by renin mRNA |
|
|
Term
| The "pre" is cleaved and leaves pro-renin. This is stored in the golgi. In the golgi the 'pro' gets cleaved leaving the active Renin. What is the enzyme that activates Renin? |
|
Definition
|
|
Term
| There is a constitutive or basal release of ____________. |
|
Definition
|
|
Term
| What are the 3 pathways that control the release of renin from the JG cells? |
|
Definition
1. Macula densa pathway
2. Intrarenal baroreceptor pathway
3. B-adrenergic receptor pathway |
|
|
Term
| In the macula densa pathway, the macula densa (part of the JGA) monitors ____________. If there is a low __________ then it will ____________ the release of renin. |
|
Definition
|
|
Term
| In the macula densa pathway, dietary Na+ restriction results in an upregulation of the inducible __________ expression. Which stimulate the release of renin. |
|
Definition
|
|
Term
| If you have ________ adenosin then renin is ____________ whereas if you have more PGE2 then renin is ________________. |
|
Definition
|
|
Term
| In the intrarenal barorecptor pathway, when does the interrenal vascular receptor in the afferent arteriole stimulate renin release? |
|
Definition
| When there is a reduced renal perfusion pressure |
|
|
Term
| ________________ is the most powerful regulator of renin release. |
|
Definition
|
|
Term
| In the B-adrenergic receptor pathway, direct stimulation of these nerves will increase renin release. What are the nerves? |
|
Definition
|
|
Term
| The B-adrenergic pathway is an _____________ pathway by which there is ________ activation of the RAS that is provoked by stimuli such as stress/posture. |
|
Definition
|
|
Term
| Describe the short loop negative feedback mechanism? |
|
Definition
Increase in renin release will increase in Ang II.
Ang II stimulates AT1 receptors on the JG cells to inhibit the release of renin. |
|
|
Term
| Describe the long loop negative feedback mechanism? |
|
Definition
| Ang II increases B.P. via the AT1 receptor which then inhibits the release of renin. |
|
|
Term
| What is the second messenger that is stimulatory to the release of renin? |
|
Definition
| cAMP (used for B-adrenergic and PGE2) |
|
|
Term
| ___________ is an inhibitory second messenger to renin release. If there is an increase in ____________ then decreased cAMP thus decreased renin release. |
|
Definition
|
|
Term
| Loop Diuretics block NaCl reabsorption so it will _____________ renin release. |
|
Definition
|
|
Term
| Which pharmacological agents decrease renin release? |
|
Definition
NSAIDs = they inhibit PG
B-blockers = inhibit adrenergic pathway |
|
|
Term
| How do ACE inhibitors and angiotensin receptor antagonist work to increase renin release? |
|
Definition
| They interrupt(block) the negative feedback loop. Not under negative control anymore |
|
|
Term
Out of all the 3 renin release pathways, which is considered to be the long term regulator?
The most powerful regulator?
Used for short term, acute regulation? |
|
Definition
Macula densa pathway
Intrarenal baroreceptor pathway
B-adrenergic receptor pathway |
|
|
Term
| ____________ is a ubiquitous enzyme found in the plasma and is mainly membrane bound predominately on ___________ and __________ cells. |
|
Definition
ACE (Angiotensin covnerting enzyme)
Endothelial
Epithelial |
|
|
Term
| What is the major physiological function of ACE? |
|
Definition
Converts Ang I to Ang II.
(from 10 A.A. to a 8 A.A) |
|
|
Term
| ACE also inactivates ______________; its preferred substrate. |
|
Definition
|
|
Term
| Which vessels are especially rich in ACE? |
|
Definition
| ACE is found on endothelial cells in the lung, brain, retina |
|
|
Term
| An alternative pathway in humans that converts Ang I to Ang II is a _____________ enzyme. |
|
Definition
Chymase
(angiotensin convertase) |
|
|
Term
| There is polymorphism to ACE that may alter risk factors for CV disease states. Individuals homozygous for the insertion polymorphism have _____________ levels of ACe in the plasma. |
|
Definition
|
|
Term
| Individuals with the DD polymorphism have ___________ circulating ACE levels and have an _____________ risk of ischemic heart disease, LVH, MI or diabetic nephropathy. |
|
Definition
|
|
Term
| Another enzyme, ACE 2, catalyzes the formation of _____________ from both Ang I and Ang II. It is a _____________ molecule. |
|
Definition
|
|
Term
| Ang 1-7 may function as an ________________ of Ang II action. |
|
Definition
|
|
Term
| AT1 and AT2 receptors are both members of the ____________. |
|
Definition
|
|
Term
| ______________ receptors mediate most of the biological effects of Ang II such as vasoconstriction, fibrosis, hypertropy, etc. |
|
Definition
|
|
Term
| AT1 Receptors can be modulated by other hormones. Which tend to increase the receptor numbers? |
|
Definition
|
|
Term
| Which hormones decrease the amount of AT1 receptors? |
|
Definition
Estrogens
Mineralocorticoids |
|
|
Term
| AT2 Receptors are widely distributed in _____________ tissue. And usually act in ____________ to the actions of AngII on AT1 receptors. |
|
Definition
|
|
Term
| Since AT2 are opposite to AT1 receptors then they are ___________ and ___________. |
|
Definition
Vasodilatory
Anti-proliferative |
|
|
Term
| How do ACEi provide CV protection? |
|
Definition
1. Block degradation of Ang 1-7 which can then inhibit Ang II actions = vasodilate, antiproliferative
2. Increases bradykinin (vasodilates)
3. Increases levels of ACE2 and Ang 1-7 |
|
|
Term
| Chronic treatment with ACEi and ARB increase plasma Ang 1-7 levels up to _______ fold. |
|
Definition
|
|
Term
| T/F: Locally formed Ang can act as growth factors, NTs and smooth muscle dilators. |
|
Definition
| False; everything is right except they act as smooth muscle constrictors. |
|
|
Term
| You can alsof ind RAS in the _____________ and ____________. |
|
Definition
|
|
Term
| After an injury on the skin, there are elevated levels of Ang II, so the RAS may be involved with _____________. |
|
Definition
|
|
Term
| There is a strong association of pancreatic function with ____________, ____________ and _____________-. |
|
Definition
Obesity
Hypertension
Diabetes |
|
|
Term
| What did the HOPE study reduce? |
|
Definition
| The incidence of diabetes |
|
|
Term
| Ang II increases total peripheral resistance--indirect and direct effects. What are some of the ways it does this? |
|
Definition
1. Direct vasoconstriction on precapillarly arterioles
2. Increase NE release, and inhibits its uptake
3. Increase sympathetic outflow
4. Increase catecholamines release from medulla
5. Increase aldosterone release from cortex
6. Enhance release of ADH
7. Dipsogenic effect (drink more) |
|
|
Term
| Ang II alters CV structures by stimulating ____________ of VSM, _____________ of VSM, or ____________ of VSM. |
|
Definition
Hypertrophy and or remodeling
Vasoconstriction
Mitogenesis |
|
|
Term
| Hypertrophy of VSM occurs both hemodynamically and nonhemodynamically. Describe both. |
|
Definition
Hemo = increase in pressure
Non = Stimulates growth factors and expression of several genes - "tissue RAS" |
|
|
Term
| Why does the RAS play a role in atherosclerosis? |
|
Definition
Oxidation of LDL
Pro-inflammatory effects |
|
|
Term
| Why is Ang II said to have pro-thrombotic effects? |
|
Definition
| It stimulates PAI-1 (plasminogen activator inhibitor) |
|
|
Term
| Normally plasminogen is converted to plasmin then plasmin degrades fibrin and breaks down clots. __________ inhibits the breakdown of the clot. |
|
Definition
|
|
Term
| What kind of pro-inflammation effects does Ang II possess? |
|
Definition
1. Increases vascular permeability via PG and endothelial growth factors
2. Recruits cells
3. Pavementation/exudative phase
4. Tissue repair |
|
|
Term
| ____________ respond to Ang II |
|
Definition
|
|
Term
| Where is aldosterone made? |
|
Definition
| In the Zona Glomerulosa of the adrenal cortex |
|
|
Term
| The secretion of aldosterone is regulated by _______________ and __________. |
|
Definition
|
|
Term
| What is the major function of Aldosterone (mineralocorticoid)? |
|
Definition
To enhance Na+ reabsorption
And excrete K+ and H+ |
|
|
Term
| What are some therapy options for hypertension? |
|
Definition
1. Renin inhibitors
2. ACEi
3. AT1R antagonist (ARB)
|
|
|
Term
| Why is ACEi and ARB contraindicated in women who are pregnant? |
|
Definition
| Because it will halt the development of the fetal kidney. |
|
|
Term
| What does the HOPE study stand for? |
|
Definition
| Heart Outcomes Prevention Evaluation |
|
|
Term
| In the HOPE study, not only was there a reduction in the new cases of diabetes, but also the use of ACEi reduced the incidence of ______________ in pateints with CV disease. |
|
Definition
|
|
Term
| How do ACEi reduce the incidence of heart attacks? |
|
Definition
1. reduce pressure on heart
2. Reduce cardiac hypertrophy
3. Decrease Ang II and hence PAI-1 (break down clots)
4. Reudce platelet action
5. Increase bradykinin levels
6. Increase Ang 1-7 and ACE 2 |
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|
