Renovascular Hypertension (RVH) part2: Pathophysiology: RAAS, Models and ischemic nephropathy

Renin-Angiotensin-Aldosterone System (RAAS)

·         Function: maintain blood volume, BP, and total body Na.

·         RAS → renal hypoperfusion → activation of RAAS → vasoconstriction, and volume expansion.

·         Continous activation of the RAAS → changes of heart and vessels.

·         Renin is a proteolytic enzyme that is released from the granules of the juxtaglomerular apparatus (JGA) by ↓ pressure of afferent arteriole.

·         Renin converts angiotensinogen → angiotensin I.

·         angiotensin-converting enzyme (ACE) convert angiotensin I → angiotensin II.

·         angiotensin II: very potent vasoconstrictor.in plasma, kidney, heart, lung and brain.

·         Angiotensin II →

Ø  release of aldosterone from the adrenal cortex, → Na reabsorption (salt&water retention) and K excretion in DCT.

Ø  activates the G-protein coupled receptor angiotensin type 1 receptor (ATR1) → V.C., upregulation of other endogenous vasoconstrictors, and ↑ Na absorption by the kidney.

Mechanism of RVH:

1.   V.C. (Angiotensin II): unilateral RAS.  

2.   Volume expansion (Aldosterone): Bilateral or solitary kidney RAS.

·         Models:

1.   Unilateral RAS → contralateral kidney ↓ Na and water absorption (compensatory mechanism for the diseased kidney) → ↓ volume expansion. HTN is due to Angiotensin II (Vasoconstrictor –Hypertensive model)

2.   Bilateral or solitary kidney RAS → no compensatory mechanism → Na and water retention → “volume-dependent” or Goldblatt HTN (Volume-Hypertensive model).

·         sustained HTN is due to:

Ø  ↑ endothelin (Local paracrine effect)

Ø  RAAS activation

Ø  oxidative stress

Ø  structural changes of the heart and arteries.

Mechanism of Ischemic Nephropathy: renal hypoperfusion.