1. The Renin-Angiotensin- Aldosterone System MATT VREUGDE M.VREUGDE@WARWICK.AC.UK

2. What is the RAAS & why do we need it?  RAAS = system of hormones that regulate blood pressure and fluid balance  Involves the kidneys, brain, liver & lungs  Can go wrong, both genetically and acquired  Presents many targets for pharmacological intervention

3. Animation TIME!!! JXA RENIN ANGIOTENSINOGEN ANGIOTENSIN I ANGIOTENSIN II ACE ALDOSTERONE Na + excretion H 2 O excretion K + excretion - - + Thirst ADH secretion ACTH secretion + + + Vasoconstriction Effective Circulating Volume Extracellular Fluid Volume Blood pressure + + + Na + / Blood flow

4. What can go wrong? Physical alteration of the system  Renal artery stenosis  Essential hypertension (reduced cardiac output) Renal tumours  Renin secreting  Phaeochromocytoma Aldosterone  Addison’s disease – adrenal insufficiency leading to hypoaldosteronism  Conn’s syndrome – primary hyperaldosteronism (aldosterone producing adenoma)  Liddle's syndrome – pseudohyperaldosteronism (don’t bother)

5. How can we use it to treat hypertension?  ACE inhibitors: ramipril  Blocks all action of ACE, including the breakdown of bradykinin, leading to a dry cough  Angiotensin II receptor antagonists: losartan  Need a higher dose and not as effective as ACE inhibitors but generally better tolerated  Mineralcorticoid receptor antagonists: spironolactone  Block action of aldosterone, increasing Na+ excretion and hence decreasing fluid retention

6. Animation TIME!!! JXA RENIN ANGIOTENSINOGEN ANGIOTENSIN I ANGIOTENSIN II ACE ALDOSTERONE Na + excretion H 2 O excretion K + excretion - - + Thirst ADH secretion ACTH secretion + + + Vasoconstriction Effective Circulating Volume Extracellular Fluid Volume Blood pressure + + + Na + / Blood flow Ramipril Losartan Aldosterone

7. Questions??