RAAS Flashcards
What are the two main processes of RAAS
- Alteration of vascular tone
- Controlling Na+ levels
What kind of enzyme is renin
Proteolytic
What stimulates renin release
- Sympathetic stimulation of beta-agonist receptors
- Decreased glomerular filtration
- Decrease in renal perfusion pressure
What does renin do
Converts angiotensinogen into angiotensin I
What does ACE do
Converts angiotensin I into angiotensin II
Where is ACE located
Primarily in endothelial cells in the lungs
What does angiotensin II do to blood vessels and via what receptors and mechanisms (2 pathways)
1) It is a potent vasoconstrictor via AT-1 receptors, a g-protein coupled receptor that increases Ca2+ levels and smooth muscle contraction
2) via increased noradrenaline from sympathetic nerves (NA another g-protein receptor ligand)
What does angiotensin II do in regards to natriuresis (2 pathways)
Stimulates aldosterone secretion which:
1) Increases apical Na+ channels
2) Aldosterone binds with mineralocorticoid receptor resulting in increased expression of ENac channels which are inserted in the basolateral membrane of cells of the collecting tubules resulting in Na+ reabsorption.
3) Increased tubular reabsorption of Na+
What are the two main drugs that target the RAAS
ACE inhibitors
Angiotensin receptor antagonists (ARBs)
More minor drugs that target RAAS (4)
Aldosterone antagonists
Calcium channel blockers
Diuretics
Beta-blockers
What does ACE-Is do and how
Mimics the section of angiotensin I that binds to ACE, binds to ACE itself and stops ACE from binding to angiotensin I (a competitive inhibitor)
What is an example of an ACE inhibitor
Cilazipril
anything that ends in ipril os probably an ACE inhibitor
What is the secondary effect of ACE inhibitors
ACE are also known as kininase II which degrades bradykinin (inflammatory mediators). Therefore ACE-Is increase bradykinin
What are two main adverse effects that stem from increased bradykinin that occur with ACE-is use
Dry cough and angioedema
Why does angioedema occur with ACE-Is use. Where does this most commonly occur?
Because of the increased levels of bradykinin which are inflammatory mediators that cause vasodilation and increased permeability.
Lips, larynx, pharynx. Can block airways!