Long-term benefit versus risk in therapeutic blockade of the renin-angiotensin system

Inhibitors of the renin-angiotensin system, which are promising therapeutic agents with few side effects, have measurably improved the management of many patients with primary or secondary hypertension and those with heart failure. This paper briefly reviews the emerging evidence for the potential risk associated with long-term inhibition of the renin system. The current lack of methodology for quantification of renin-angiotensin inhibition in various tissues, however, precludes firm conclusions. Preliminary evidence suggests that in functional terms, a downregulation of the renin-angiotensin system, if therapeutically successful, is safer than aggressive and longer-lasting inhibition. It has been questioned whether antihypertensive therapy 'normalizes' the structural cardiovascular changes and whether interference with the initial adaptive phase may prove detrimental. However, no specific role for renin inhibition, apart from the antihypertensive effect, has yet been defined.