Organic anion transporter 3 inhibitors as potential novel antihypertensives.

Hypertension is an exceedingly common disease with potentially devastating complications. Unfortunately, existing treatments are often only partially effective, indicating the utility of the development of novel therapeutics. It has recently been discovered that loss of renal organic anion transporter 3 (Oat3) results in decreased blood pressure. This suggests (regardless of the underlying mechanisms, which are, as yet, unclear) that inhibition of Oat3 function might also decrease blood pressure, and, therefore, that inhibitors of Oat3 might serve as novel drugs in the treatment of hypertension. In support of this hypothesis, it has been found that at least some potent Oat3 inhibitors can lower blood pressure. These recent findings are discussed in the context of the alternating access model that has been proposed for organic anion transporter function, with particular attention to the little-appreciated phenomenon of trans-inhibition.