1. Renal autacoids
Domina Petric, MD

2. Renal autacoids are
Adenosine
Prostaglandins
Peptides

3. Adenosine Adenosine is an unphosphorylated ribonucleoside.
Renal adenosine concentrations rise in response to hypoxia and ATP consumption.
Hypoxia results in compensatory vasodilation.
If cardiac output is sufficient, hypoxia causes increased blood flow.
Increased blood flow leads to an increase in glomerular filtration rate (GFR) and greater solute delivery to the tubules.

4. Adenosine
This increased delivery would increase tubule work and ATP consumption.
In the hypoxic kidney, adenosine decreases blood flow and GFR.
Medulla is always more hypoxic than the cortex: adenosine increases Na+ reabsorption from the reduced flow in the cortex.

5. Adenosine Adenosine receptors are A1, A2a, A2b and A3.
A1 receptor is found on the pre-glomerular afferent arteriole, as well as the proximal convoluted tubule (PCT) and most other tubule segments.

6. Adenosine
Adenosine affects ion transport in the PCT, the medullary thick ascending limb (TAL) and collecting tubules.
Adenosine reduces blood flow to the glomerulus and GFR via the A1 receptors on the afferent arteriole.
It is the key signaling molecule in the process of tubuloglomerular feedback.

7. Adenosine
Adenosine significantly alters Na+ transport in several segments.
In the proximal tubule, adenosine has a biphasic effect on NHE3 acitivity:
enhancement at low concentrations
inhibition at very high concentrations

8. Adenosine
Adenosine receptor antagonists block the enhancement of NHE3 activity and exhibit diuretic activity.
Adenosine antagonists do not cause wasting of potassium.
Adenosine A1 receptors are also present in the collecting tubule.

9. Prostaglandins
Five prostaglandin subtypes are PGE2, PGI2, PGD2, PGF2α and thromboxane (TXA2).
All are synthesized in the kindey and have receptors in this organ.
PGE2 blunts Na+ reabsorption in the TAL of Henle´s loop and ADH-mediated water transport in collecting tubules.

10. Prostaglandins
These actions of PGE2 contribute significantly to the diuretic efficacy of loop diuretics.
Blockade of prostaglandin synthesis with NSAIDs can interfere with loop diuretic activity.

11. Peptides ANP and BNP are synthesized in the heart.
CNP comes primarily from the brain.
Vascular effects and sodium transport effects in the kidney: natriuresis.

12. Peptides It is made in distal tubule epithelial cells.
Urodilatin is structurally very similar to ANP, but it is synthesized and functions only in the kidney.
It is made in distal tubule epithelial cells.
Urodilatin blunts Na+ reabsorption through effects on Na+ uptake channels and Na+/K+-ATPase at the downstream collecting tubule system.

13. Peptides
Urodilatin reduces glomerular afferent and increases glomerular efferent vasomotor tone through effects on vascular smooth muscle.
These effects cause an increase in GFR, which adds to the natriuretic activity.

14. Peptides
Ularitide is a recombinant peptide that mimics the activity of urodilatin.
Intravenous ularitide can dramatically improve cardiovascular parameters and promote diuresis without reducing creatinine clearance.

15. Peptides
The cardiac peptides ANP and BNP have pronounced systemic vascular effects.
The receptors ANPA(NPRA) and ANPB (NPRB) are transmembrane molecules with guanylyl cyclase catalytic activity at the cytoplasmic domains.

16. Peptides
Both ANP and BNP increase GFR through effects on glomerular arteriolar vasomotor tone.
They also exhibit diuretic activity.
CNP has little diuretic activity.
Nesiritide (BNP) may enhance the activity of other diuretics.
Carperitide is ANP.

17. Katzung, Masters, Trevor. Basic and clinical pharmacology.
Literature
Katzung, Masters, Trevor. Basic and clinical pharmacology.