Flashcards in 37 RAS Deck (28)
Endogenous peptides play an important role in normal cardiovascular and fluid homeostasis. What do they interact with?
1. Effector organs
2. Peripheral nervous system
3. CNS via circumventricular organs
What are the 3 CVOs?
organum vasculosum of the lamina terminalis
What converts angiotensinogen to angiotensin I? angiotensin I to angiotensin II? and on to III?
What receptors does angiotensin I and II act on? III?
At2R and AT1R
What receptor does angiotensin 1-7 act on?
T-F there is a route from angiotensin1 to angiotensin (1-7) that does not use ACE?
The classical ACE-AII-AT1 receptor axis is known to cause what?
stroke, hypertension and cardiovasc. events
What are the 4 mechanisms by which renin secretion is controlled?
1. Renal vascular receptor- low stretch inc renin
2. Macula densa receptor- low na inc renin
4AII, AVP, K all inhibit renin release (negative feedback)
What to mechanisms increase renin release in regards to lower arterial pressure?
1. renal baroreceptors
2. Systemi baroreceptors through SNa
What are the 3 things that stimulate Renin release?
1. lowered arterial pressure
2. Dehydration, hemorrhage
What are the 4 actions that raises arterial pressure from angiotensin?
1. direct vasoconstriction in smooth muscle
2. CNS up SNa and Vasopressin release
3. Norepinephrine release from sympathetic neurons
4. Adrenal medulla stim release of epi
Can angiotensin peptides cause hypertrophy?
Yes, by hemodynamic and non-hemodynamic mechanisms
What does angiotensin stimulate in the CNS? adrenal?
Thirst, and ACTH from pituitary
How is R?A system detrimental to the heart? what counteracts?
heart failure diminishes renal flow, renin up, AII up leads to increased peripheral resistance (after load) and increased H2O (preload)---thus exacerbating the condition.
angiotensin (1-7) counteracts
How does angiotensin promote sodium retention? regulate its own production?
1. vasoconstriction and incr. proximal tubular Na reabsorption
2. decr. renin release neg feedback
What is the outcome of AT1R activation? AT2R?
1. Gq--> stim phospholipase C--> up Ca, MapK- vasoconstriction
2. Does not activate above-- incr. NO and blocks MAPK- vasodilation (may be beneficial for AT1R blockers, AII effects are much stronger on AT1R vasoconstriction)
What does the MAS receptor mediate? stimulates what?
vasodilation, anti-inflammatory, anti-cell prolix, stimulates up Ca and NO
What do ARBs have higher affinity for? do the affect kininase II? blockade results in loss of what?
3. AII feedback inhibition of renin release from kidney
Ang(1-7) is promoted from extra angiotensin I when ACE is blocked. What other mechanisms increase Ang-(1-7) when ACE is blocked?
Degradation of Ang(1-7) by ACE is also impaired
RAS blockade has little effect in normotensive patients, except for what occasion?
Na depleted individuals
Where is RAS produced/used on a local bases?
vascular smooth muscle
What does plasma kallikrein activate? tissue kallikrein?
What are kinin's effects on arterioles ? When? large arteries?
1. a. vasodilation via NO and eicosanoids, b. incr. capillary permeability, c. stim SNa, d. stimulate EPI
2. in hypertensive situations, but not for maintenance
3. constrict large arteries and veins
Does bradykinin promote inflammation? pain? receptor?
yes and yes, GPCR B2 [up PLC increase Ca, up PLA2 increase eicosanoids]
Do ACE inhibitors decrease bradykinin half life?
No they increase it
When is vasopressin released?
low arterial P, low fluid volume or high plasma osmol, pain/nausea/hypoxia
Physiologic actions of vasopressin?
2. direct vasoconstriction (reflex bradycardia)
3. indirect central actions--activate vagal--> bradycardia