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 inhibitors nor angiotensin II (Ang II) antagonists are likely to trigger responses similar to ACE inhibitor-induced involvement of kinins, prostaglandins, or nitric oxide. Several observations suggest species variation in the contribution of these pathways to the renal response to ACE inhibition. In humans, recent investigation suggests that virtually all of the renal response is due to a fall in Ang II formation. Perhaps most persuasive is the surprising observation that the renal hemodynamic response to renin inhibitors exceeds by more than 50% 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 inhibitors, better tissue penetration of these highly lipophilic agents, or more effective blockade of Ang II formation through an action at the rate-limiting step or non-ACE-dependent Ang II generation. Substantial evidence favors the latter two possibilities. Whatever the explanation, these observations raise the intriguing possibility that the undoubted therapeutic efficacy of ACE inhibition in renal injury, documented most rigorously for type I diabetes mellitus, might be exceeded with the newer classes of agent.
Hollenberg
N K
NK
Brigham and Women's Hospital, Boston, MA 02115, USA.
Fisher
N D
ND
D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000502:physiology*; D000092502:Renin Inhibitors
D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D000092502:Renin Inhibitors