Renin-angiotensin system Flashcards
Angiotensin II
Acts at AT1 receptor Is a pressor agent - increases BP Leads to aldosterone secretion Increases hypertrophy/hyperplasia Increases fibrosis Increases oxidative stress.
Angiotensin 1-7
Counteracts actiins of angiotensin II. Vasodilator Acts at Mas (GPCR) receptor. Decreases hypertrophy/hyperplasia Decreases fibrosis Decreases oxidative stress
Rate limiting step of angiotensin II synthesis
The rate limiting step is the presence of renin
Renin is released from juxtaglomerular cells lining the afferent arterioles of the kidney.
Renin release is controlled by bp, salt intake, and angiotensin II.
Local control of renin release
Intra-renal
Decreased renal perfusion pressure leads to increased renin secretion.
Immediate stimulus is a decrease in wall tension of afferent arterioles.
Decreased tubular sodium concentration also increaees renin secretion.
CNS control of renin secretion
Decreased systemic BP leads to increased renin release.
Involves barorecptor reflex
Sympathetic nerves directly innervate JG cells.
NA activates B1 adrenoceptors in JG cells.
Actions of angiotensin II
Homeostatic role - control of BP, fluid volume, electrolyte balance. Stimulates aldosterone production to increase renal reabsorption of Sodium and water.
Cardiovascular actions - AT1 receptor mediated, direct contractile action on vascular smooth muscle, stimulates Adr release from adrenal medulla, prejunctional increased output of NA from sympathetic nerves.
Renal hypertension
About 10% of hypertension cases.
Due to overactivation of the Renin-angiotensin-aldosterone system.
Inhibition of the RAAS
Renin inhibitors Inhibition of renin release Inhibition of ACE AT1 receptor block Aldosterone receptor antagonist
Renin inhibitors
Aliskiren - orally active
Inhibits rate limiting step
Inhibition of renin release
Beta-blockers (propanolol)
Block sympathetic drive to JG cells
Incomplete inhibition of release as intra-renal control is not affected.
Inhibition of ACE
Captopril,enalopril
Competative ACE inhibitors
Irritant cough due to inhibition of bradykinin hydrolysis
Useful in most forms of hypertension, not just renal hypertension.
Prolong life in heart failure.
Decrease TPR, decreases production of aldosterone, decreases sodium and fluid retention.
AT1 Receptor block
Losartan, valsartan
Competatjve inhibitor
Orally active (not a peptide)
Used for hypertension and heart failure, no irritant cough.
Aldosterone receptor antagonist
Spironolactone
Synthetic steroid, competative antagonist of aldosterone.
Inhibits reabsorption of Sodium and water in renal collecting ducts.
Potassium sparing diuretic.
Used in hearg failure where there is massive over-reactivity of RAAS.
