[Angiotensin II receptor-mediated function unmasked by gene-engineered animals].
The receptors for angiotensin (Ang) II are classified into two subtypes (AT1-R and AT2-R) by the discovery of non-peptidic ligands and AT1-R mediates most of the cardiovascular actions of Ang II. AT2-R is expressed at very high levels in the developing fetus, whereas in the adult its expression in the cardiovascular system is very low. Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. AT2-R also activates the kinin/nitric oxide/cGMP system in the cardiovascular and renal system, resulting in the AT2-R-mediated cardioprotection, vasodilation and pressure natriuresis. These effects transmitted by AT2-R are mainly exerted by stimulation of protein tyrosine or serine/threonine phosphatases in Gi-protein dependent manner. The expression level of AT2-R is much higher in human hearts than in those of rodents, and the AT2-R-mediated actions are likely enhanced, especially by clinical application of AT1-R antagonists.
Matsubara
H
H
Department of Medicine II, Kansai Medical University.
Iwasaka
T
T
D000328:Adult; D000818:Animals; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D011945:Receptors, Angiotensin / Q000235:genetics / Q000502:physiology*
D011945:Receptors, Angiotensin