RENAL CIRCULATION AND BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM - IS ANGIOTENSIN-CONVERTING ENZYME INHIBITION THE LAST WORD

The mechanism by which angiotensin-converting enzyme (ACE) inhibition influences renal perfusion and function has assumed growing importance as alternatives for blocking the system have emerged. Neither renin i nhibitors nor angiotensin II (Ang II) antagonists are likely to trigge r responses similar to ACE inhibitor-induced involvement of kinins, pr ostaglandins, or nitric oxide. Several observations suggest species va riation in the contribution of these pathways to the renal response to ACE inhibition. In humans, recent investigation suggests that virtual ly all of the renal response is due to a fall in Ang II formation. Per haps most persuasive is the surprising observation that the renal hemo dynamic response to renin inhibitors exceeds by more than 50% the resp onse to ACE inhibition in healthy humans. To the extent that kinins or prostaglandins contribute to the renal response to ACE inhibition, on e would anticipate a smaller response to renin inhibition. Possible ex planations include an unanticipated additional action of renin inhibit ors, better tissue penetration of these highly lipophilic agents, or m ore effective blockade of Ang II formation through an action at the ra te-limiting step or non-ACE-dependent Ang II generation. Substantial e vidence favors the latter two possibilities. Whatever the explanation, these observations raise the intriguing possibility that the undoubte d therapeutic efficacy of ACE inhibition in renal injury, documented m ost rigoroursly for type I diabetes mellitus, might be exceeded with t he newer classes of agent.