Test 2: lecture 24 RAAS Flashcards
steps of RAAS
angiotensinogen (renin) → angiotensin I (ACE) → angiotensin II
ACE is a nonspecific enzyme that cleaves — from diverse substrates like —
dipeptides
bradykinin, angiotensin 1
angiotensin III is formed by — and will cause — release
angiotensin II (ACE)
aldosterone release
how does angiotensin degraded
angioteninases
enzyme breaks angiotensin down in 15-60 seconds
aldosterone will —
cause Na and water retention
what does angiotensin do
will cause vasoconstriction→ increases BP
causes aldosterone secretion → retension of water and Na from urine
what triggers aldosterone release
increased angiotensin II, ACTH, low Na, high K
acidosis
atrial stretch receptors in response to low BP
aldosterone causes retention of Na and water, made by the zona glomerulosa of the adrenal gland
aldosterone is made by —
zona glomerulosa cells in the adrenal cortex
effects of RAAS on cardiovascular system
vasoconstriction
increased cardiac contractility with little change in heart rate
cause HTN/ fix low BP
effect of RAAS on ANS
SYM: causes release of NE and enhances sensitivity of target tissues to NE
Adrenal medulla: causes release of catecholamines from chromaffin cells (↑ epi)
RAAS effect on CNS
increase SYM
cause pituitary to release ADH and ACTH
cause increased thirst and need for salty things
effect of RAAS on cell growth
cause cardiovascular hypertrophy
overall effect of RAAS on the body
AT1 receptors mediate —
most of the known functions of angiotensin
will cause smooth muscle contractions in seconds
GPCR receptor
losartan works on what type of receptor
angiotensin 1 (AT1) receptor
two major ways to block RAAS
ACE inhibitors
angiotensin II receptor blockers (ARBs)
benefits of ACE inhibitiors
stops formation of angiotensin II
- decrease systemic vascular resistance without increasing heart rate
- promote natriuresis (pee out Na)
- treatment of hypertension, decrease mortality and morbidity in heart failure and left ventricular dysfunction after myocardial infarction
- delay diabetic nephropathy
what are some side effects of ACE-inhibitors
will inhibit degradation of other substances (bradykinin and substance P)
cough
angioedema
ACE not specific for only angiotensin
captopril
ACE inhibitor
will ↓BP and treat CHF
what are some ACE inhibitors
enalapril, captopril, lisinopril
ACE-I= -pril
losartan
nonpeptide antagonist of angiotensin 1 (AT1) receptor
does not effect AT2
used to treat HTN
what are some ARBs
angiotensin receptor blockers/antagonists
peptide congeners: work in theory
nonpeptide antagonist: losartan, Azilsartan (Edarbi), Candesartan (Atacand), Eprosartan
ARBs — sartan
angiotensin vs bradykinin
angiotensin: works to raise blood pressure
bradykinin acts to lower blood pressure (vasodilation)
how to form kinins
kiniogens (kinogenases/kallikreins) →kinins
tissue damage and infections activate this class of compounds.
kallikrein-kinin system =KKS
where do kallikreins come from
made in liver as prekallikreins
cleaved to active kallikrein
kallikrein will bind to kininogens to form kinins
where to find kininogens
plasma, lymph , intersititial fluid
in plasma: there are a high and low molecular weight versions
high: stays in bloodstream
low: can cross capillary walls into tissues
what is the major form of kinins in plasma
bradykinin
kininase II is the same as
ACE
both work on many peptides: kinins and angiotensin
which kinin receptor works on bradykinin and kallidin and what does it cause
B2 receptor
a BGCR
will cause vasodilation and excretion of Na and pain
B2 kinin receptors will bind to — and cause —
bradykinin and kallidin
Vasodilation, Na+ excretion, pain
B1 kinin receptors binds to — and cause —
des-Arg kinins (NOT bradykinin)
Vasoconstriction, pain, leukocyte recruitment
what type of receptor has opposite effect as angiotensin 1 receptors
bradykinin B2 receptors
B2 cause vasodilation and Na excretion
AT1 cause vasoconstriction and Na retention
why are ACE inhibitors cardioprotective
ACE inhibitors will block angiotensin II formation and will also prevent the breakdown of bradykinin
ACE inhibitors will decrease BP and work to treat CHF (by getting rid of Na)