New insights into carbonic anhydrase inhibition, vasodilation, and treatment of hypertensive-related diseases.

Carbonic anhydrase (CA) and its inhibitors are relevant to many physiological processes and diseases. The enzyme is differentially expressed throughout the body, in concentration and subcellular location, and as 13 catalytically active isoforms. Blood vessels contain small amounts of CA, but the enzyme's role in vascular physiology and blood pressure regulation is uncertain. However, considerable recent evidence points to vasodilation by CA inhibitors. CA inhibition in vascular smooth muscle, endothelium, heart, blood cells, and nervous system could all contribute. It is equally plausible that other targets besides CA for all known CA inhibitors may account for their vascular effects. I will review this knowledge and important remaining gaps relating to treatment of hypertensive-related diseases with potent sulfonamide inhibitors, such as acetazolamide; but also the possibility that CA inhibition by thiazides and loop diuretics, although generally weaker, may have antihypertensive effects beyond their inhibition of renal sodium transporters.