Angiotensin II and Thirst: Therapeutic Considerations

Angiotensin II is the effector peptide of the renin‐angiotensin system and is involved in a wide range of physiologic functions that relate to volume control. In this regard, angiotensin II maintains and regulates salt and water balance, is critically involved in cardiovascular function, and governs thirst. When present in excess, angiotensin II can pathologically influence each of these functions. The role of angiotensin II in controlling sodium balance, in both renal insufficiency states and congestive heart failure, is clearly recognized. Alternatively, it is poorly appreciated that angiotensin II plays an important role in both normal and pathologic thirst states. The latter is a potential problem in both end‐stage renal disease and congestive heart failure. Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (AT 1 ‐RAs) have both been shown to reduce abnormal thirst drive. Whether an ACE inhibitor or an AT 1 ‐RA lessens thirst drive to any significant degree relates to its capacity to penetrate the blood‐brain barrier. Head‐to‐head comparisons of ACE inhibitors and AT 1 ‐RAs, as to their effect on thirst drive, have not been undertaken in a systematic fashion; thus, until otherwise established, the effect of these compounds on thirst should be viewed as a class effect, albeit one that is likely to be dosedependent.