Inhibitory effect of antihypertensive drugs on calcineurin in cardiomyocytes

In recent years, a handful of research investigations have shown that some antihypertensive drugs, i.e., angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB), can inhibit myocardial expression and/or activity of calcineurin. Calcineurin is a Ca²⁺-calmodulin-dependent serine/threonine phosphatase and is a target for some immunosuppressive drugs. It is well known that traditional immunosuppressants, such as cyclosporine A (CsA) and tacrolimus (FK506), are anticalcineurin, and their prohypertensive effects are such that antihypertensive therapy is often required in organ transplant recipients who receive these drugs. Therefore, the idea that ACEI, ARB, and CCBs are both antihypertensive and anticalcineurin seems paradoxical. This invited review tries to summarize these new findings and analyze the scientific and clinical significance of these claims. The review also emphasizes some of the shortcomings in these studies and some questions that need to be addressed in future investigations.