From the Guidelines
Angiotensin II increases bicarbonate reabsorption in the kidneys through its effects on sodium-hydrogen exchangers and basolateral sodium-bicarbonate cotransporters, as well as its stimulation of H+-ATPase pumps and aldosterone production, which collectively help maintain acid-base balance and regulate blood pH. The primary mechanism by which angiotensin II increases bicarbonate reabsorption involves the stimulation of sodium-hydrogen exchangers (NHE3) in the proximal tubule, promoting hydrogen ion secretion into the tubular lumen while simultaneously reabsorbing sodium 1. When hydrogen ions combine with filtered bicarbonate, they form carbon dioxide and water through the action of carbonic anhydrase. This carbon dioxide then diffuses back into tubular cells where it is converted back to bicarbonate and returned to the bloodstream. Additionally, angiotensin II enhances the activity of basolateral sodium-bicarbonate cotransporters, directly facilitating bicarbonate reabsorption, and stimulates H+-ATPase pumps in the collecting ducts, further promoting acid secretion and bicarbonate recovery 1. Some key points to consider in this process include:
- The role of angiotensin II in maintaining GFR during states of significant volume depletion, as noted in studies on renal considerations in angiotensin converting enzyme inhibitor therapy 1
- The pathophysiological mechanisms by which angiotensin II preserves GFR in the face of reduced cardiac output, while also causing avid renal salt retention in patients with CHF 1
- The importance of considering the renal actions of angiotensin II in the context of its overall effects on the body, including its central dipsogenic effect and ongoing secretion of arginine vasopressin, which can result in hyponatremia in CHF patients 1.
From the Research
Mechanism of Angiotensin II-induced Bicarbonate Reabsorption
- Angiotensin II stimulates bicarbonate reabsorption in the proximal tubule by increasing the activity of the sodium/hydrogen exchanger and the sodium/bicarbonate cotransporter 2, 3.
- The effects of angiotensin II on bicarbonate reabsorption are mediated by angiotensin II receptors on the basolateral membrane of the proximal tubule 3.
- Luminal angiotensin II also stimulates bicarbonate reabsorption, and luminal angiotensin II levels are 100 to 200-fold higher than that found in plasma 3.
- Angiotensin II reduces bicarbonate permeability and causes alteration in the apparent substrate affinity, but not maximal capacity, of the proximal hydrogen ion secretory system involving the Na+/H+ antiporter 4.
Transporters Involved in Angiotensin II-induced Bicarbonate Reabsorption
- Na+/H+ exchange: angiotensin II increases the rate of luminal Na+/H+ exchange approximately 3.5-fold 2.
- Na+/HCO3- cotransport: angiotensin II increases the rate of basolateral Na+/HCO3- cotransport approximately 2.5-fold 2.
- H+-ATPase: angiotensin II regulates H+-ATPase activity in intercalated cells of the collecting tubule 5.