Renal responses to antagonism of the renin-angiotensin system.
Detailed knowledge is becoming available on the intrarenal renin-angiotensin system. This paper briefly describes some recent developments on the intrarenal formation and compartmentalization of components of the renin-angiotensin system. Furthermore, renal responses to angiotensin II are reviewed with respect to intraluminal angiotensin II concentrations, and interactions with nitric oxide on the afferent arteriole and the tubuloglomerular feedback system. A main issue is whether angiotensin-converting enzyme inhibitors can block the intrarenal renin-angiotensin system to the same extent as in other tissues. This is particularly interesting in view of the recently discovered polymorphism in the angiotensin-converting enzyme gene, which accounts for substantial variation in plasma angiotensin-converting enzyme levels. AT1 receptor antagonists are now available for clinical use. Although the AT1 receptor has been reported to mediate most, if not all, of the renal actions of angiotensin II, these compounds differ from angiotensin-converting enzyme inhibitors. Firstly, AT1 receptor blockers lack the prostaglandin- and kinin-potentiating effects of angiotensin-converting enzyme inhibitors. Furthermore, they increase angiotensin II, which can activate non-AT1 receptors. Finally, the pharmacodynamics of AT1 receptors may evoke different responses from the sympathetic nervous system than those of angiotensin-converting enzyme inhibitors. Currently, it is unclear whether renin inhibitors will have advantages over angiotensin-converting enzyme inhibitors or AT1 receptor antagonists. From the recent research, it is clear that the classical concept of the renin-angiotensin system cannot be pursued, and is being replaced by detailed schemes in which the intrarenal renin-angiotensin system has an important place.
Braam
B
B
Department of Nephrology and Hypertension, Utrecht, Netherlands.
Koomans
H A
HA
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II