Cardiovascular and renal function of angiotensin II type-2 receptors.
While all of the well-known cardiovascular and renal effects of angiotensin II (ANG) are attributed to the ANG type-1 (AT(1)) receptor, much less is known about the function of ANG type-2 (AT(2)) receptors. This review focuses on progress made in AT(2) receptor research over the past 10 years mainly enabled by the availability of AT(2) receptor-deficient mice. Two general mechanisms regarding AT(2) receptor-mediated actions emerge from recent experiments. Firstly, AT(2) receptor stimulation inhibits growth and promotes apoptosis, an important mechanism during development and tissue remodeling. Secondly, ANG stimulates the release of nitric oxide (NO)/cGMP via AT(2) receptor activation, as described in the aorta, heart, and kidney. This effect appears to be indirectly mediated by the modulation of bradykinin release. Thus, activation of AT(2) receptors may be potentially protective and appears to oppose the effects mediated by AT(1) receptors. The question whether AT(2) receptors are activated in patients with elevated ANG levels when treated with AT(1) receptor antagonists and whether these effects are relevant awaits further clarification.
Jöhren
Olaf
O
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, D-23538 Luebeck, Germany. joehren@uni-luebeck.de
Dendorfer
Andreas
A
Dominiak
Peter
P
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D017209:Apoptosis; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D009569:Nitric Oxide; D006152:Cyclic GMP