L5. Renin-Angiotensin-Aldosterone system Flashcards
What is the physiological role of RAAS
Synergistically with SympNS to increase blood pressure by increasing vascular tone and salt and water retention (to increase B volume)
What is each part of RAAS
Renin: proteolytic enzyme produced in the juxtaglomerular cells in response to symp stimulation.
1. Catalyses conversion of angiotensiogen to angiotensin I.
- Angiotensin I is converted by ACE in the lungs, to angiotensin II which is vasoconstrictor.
- More cleavage, Angiotensin 3 promotes
Aldosterone secretion–> Na+ retention
How does angiotensin II cause vasoconstriction and what are other agonists of this
Angiotensin 2, NA, or histamines via AT1 g coupled receptor
increases intracellular Ca2+ in vascular SM= contraction.
Also triggers release of NA from symp which can vasoconstrict using alpha receptor and increases tubular Na+ re absorption
How does aldosterone act to increase Na+ retention in collecting tubule
Binds to aldosterone mineralocorticoid receptors-intracellular receptor- in the collecting tubule. Increases synthesis of apical Na+ channels and basolateral Na+/K+ ATPase. This helps to make water travel same way.
What is an ACEnzyme inhibitor: example, action, therapeutic use and side effects
Cilazipril: mimics angiotensin 1 binding site to decrease production of angiotensin 2 to decrease blood pressure.
ACE also degrades bradykinin so inhibiting this also causes side effects: dry cough and angioedema- swelling in larynx, pharynx and lips due to vasodilation and increased permeability- hard to breathe.
These side effects fought by receptor or synthesis blockers
What is an Angiotensin Receptor Blocker: example, action, therapeutic use and side effects
Losartan: competitive antagonist at AT-1 receptors, blocking the activity of RAAS (vascular growth, vasoconstriction, aldosterone tubular Na+ reabsorption)
Which should you use ACEnzyme inhibitor or Angiotensin receptor blocker? And why not both?
ACE inhibitor is more effective but more side effects so ARB is alternative. Both decrease CVS event likelihood. Not given together dangerous- renal toxicity and increased risk of hyperkalemia
What is an Aldosterone antagonist example, action, therapeutic use and side effects
Spironolactone: antagonist at mineralocorticoid receptor, inhibits Na+ reabsorption promoted by aldosterone.
What is a Calcium channel blocker example, action, therapeutic use and side effects
Verapamil or nifedipine: Blocks Ca2+ channel so can’t trigger the same amount of Ca2+ transient for depolarisation, so less contraction= Vasodilation, decreased blood pressure
What is diuretic example, action, therapeutic use and side effects
Promote the excretion of fluid by stopping sodium reabsorption. Eg. Amiloride blocks the sodium channels up regulated by aldosterone, keeping sodium in the tubule.
Osmotic diuretics help to balance osmolarity so water is not reabsorbed with Na+
What is beta blockers example, action, therapeutic use and side effects
Metaprolol: competitive antagonist at primarily B1 adrenergic receptor to block Symp activation of heart-decrease cardiac contractility and blocks receptors at the kidney to decrease renin secretion.
