Aldosterone

For our beloved student

1. Aldosterone and Aldosterone antagonists Dr. Haji Bahadar,PhD Assistant Professor KMU-IPMS

2. Lecture outlines What is aldosterone? What is the physiological role of aldosterone? How aldosterone is controlling blood pressure?, Renin - angiotensin -aldosterone axis What is aldosterone antagonist?

3. What is aldosterone? It is a steroid hormone synthesized in the zona glomerulosa of the adrenal cortex responsible for electrolyte( sodium, chloride, and potassium ) and fluid balance in the body. Therefore, Aldosterone is known a mineralocorticoid hormone. aldosterone

4. What is the physiological role of aldosterone? Increase the absorption of Na + in: Distal renal tubules (the main effect). Salivary glands Gastrointestinal mucosa(colon) Increased renal secretion of K + .

5. Who regulate aldosterone secretion? Angiotensin II is the most important regulator and acts a major stimulus of aldosterone secretion. Hyperkalemia (increased potassium level in blood)

6. Mechanism of action

7. Mechanism of action Binding of aldosterone with the receptors initiates DNA transcription, initiating transcription of specific proteins resulting an increase in the number of sodium channels Na + -K + - ATPase molecules.

8. What is angiotensin and how it is synthesized? Angiotensin is a peptide hormone. The precursor for angiotensin is angiotensinogen ( glycoprotein) synthesized and released by the liver. Angiotensinogen is converted to angiotensin I (10 amino acid peptide) by renin (enzyme) synthesized by the juxtaglomerular apparatus of the kidney. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme(ACE). The release of angiotensinogen from the liver is stimulated by cortisol , and estrogens. Renin release from the kidney is stimulated by ECF(Effect of extracellular fluid) depletion, by low serum sodium concentrations, and by decreases in blood pressure. ACE is present mainly in the capillaries of the lungs but can also be found in endothelial and kidney. 

9. Functions of angiotensin Angiotensin also stimulates the release of aldosterone Vasoconstriction and a subsequent increase in blood pressure

10. How aldosterone is controlling blood pressure ? Aldosterone is closely linked to renin and angiotensin, which create the renin -angiotensin-aldosterone system or axis. In a healthy individual, the renin -angiotensin-aldosterone system functions without interference, helping to regulate and control blood pressure levels naturally. This system is activated when the body experiences a decrease in blood flow to the kidneys, such as after a drop in blood pressure, or a significant drop in blood volume after a hemorrhage or serious injury. Renin is responsible for the production of angiotensin, which then causes the release of aldosterone. Once the body is rehydrated and has proper salt levels in the blood, renin levels fall.

11. ACE inhibitors

12. Renin -angiotensin-aldosterone axis

13. Aldosterone antagonists and ACE inhibitors Aldosterone antagonists( spironolactone Aldactone , eplerenone ;   INSPRA ): They are also known as “potassium sparing diuretics”. They block the action of aldosterone inhibiting the reuptake of sodium and water. Normally, when sodium is reabsorbed it is exchanged with potassium which is then excreted. Since aldosterone inhibition decreases sodium reabsorption , it also decreases potassium excretion resulting in higher serum potassium levels. ACE inhibitors:   captopril ( capoten ),  enalapril ( Vasotec ),  lisinopril ( Lispril ),   quinapril ( Accupril ),  ramipril ( Ramipace ). 

14. Mechanism of action spironolactone Spironolactone is a competitive antagonist for aldosterone on its intracellular receptors

15. Angiotensin-converting enzyme (ACE) inhibitors block the formation of angiotensin II causing constriction of  blood vessels. ACE inhibitors cause the Blood vessels to relax and widen making the blood flow through easier resulting decrease in blood pressure. These medicines also increase the release of water and sodium to the urine, which also lowers blood pressure.