These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacologic interruption of the renin-angiotensin system and the kidney: differential responses to angiotensin-converting enzyme and renin inhibition.
    Author: Hollenberg NK.
    Journal: J Am Soc Nephrol; 1999 Jan; 10 Suppl 11():S239-42. PubMed ID: 9892171.
    Abstract:
    Pharmacologic interruption of the renin-angiotensin system has played a crucial role in determining its contribution to physiology, pathophysiology, and has made an enormous contribution to therapeutics. Despite this record of success, no pharmacologist would have chosen the angiotensin-converting enzyme (ACE) step for pharmacologic blockade. As renin is rate-limiting in the cascade and has remarkable specificity for its substrate, renin inhibition would have made a far more attractive target. Indeed, evidence reviewed in this article supports this case. A renin inhibitor developed to block rat renin produced a larger reduction in plasma angiotensin II concentration than did two ACE inhibitors at the top of their dose-response relationship. In humans, renin inhibition led to a larger increase in renal plasma flow in healthy human volunteers studied on a low salt diet to activate the renin system than did ACE inhibitors. Again, the studies used doses in each case at the top of the dose-response relationships for renal hemodynamics. Because the response to AT1 receptor blockade was very similar to the response induced by renin inhibitors, the results suggest that both classes of agent acted via their influence on the renin system. Moreover, the data suggest that 30 to 40% of angiotensin II formation influencing the kidney in the healthy human during renin system activation is formed via renin-dependent, but ACE-independent, pathways. These findings have potentially important therapeutic implications, and certainly help to justify the major therapeutic trials now ongoing and planned.
    [Abstract] [Full Text] [Related] [New Search]