The kidney and pharmacological interruption of the renin system: is ACE inhibition the last word?

The mechanism by which ACE inhibition influences renal perfusion and function has assumed growing importance as alternatives for blocking the system have emerged. Neither renin inhibition nor Ang I antagonists are likely to trigger a response involving kinins or prostaglandins. Several observations suggest species variation in the contribution of these pathways to the renal response to ACE inhibition. In humans, two lines of investigation suggest that virtually all of the response is due to a fall in Ang II formation. Perhaps most persuasive is the surprising observation that the renal response to renin inhibitors exceeds the response to ACE inhibition in healthy humans. To the extent that kinins or prostaglandins contribute to the renal response to ACE inhibition, one would anticipate a smaller response to renin inhibition. Possible explanations include an unanticipated additional action of renin inhibition, better tissue penetration, or more effective blockade of Ang II formation. Substantial evidence favors the latter two possibilities. Whatever the explanation, these observations hold out hope that the undoubted therapeutic efficacy of ACE inhibition in renal injury might be exceeded with the newer classes of agent.