title: Angiotensin II and endothelin induce inflammation and thereby promote hypertension-induced end-organ damage.
abstract: Angiotensin (Ang) II and endothelin (ET-1) can both be regulated by NF-kappaB. They are, to variable degrees, also capable of activating NF-kappaB and increase the expression of NF-kappaB-dependent genes. Ang II-related vascular effects are in part mediated by ET-1. Nitric oxide synthase inhibition facilitates Ang II-related effects, which can be inhibited both by AT1-receptor blockers and by endothelin system inhibitors. This state-of-affairs supports the notion that a combined therapeutic strategy of inhibiting Ang II and ET-1 generation or blocking their effects at the receptor level would be superior to either strategy alone. Animal studies are encouraging but not without conflicting results. Angiotensin-converting enzyme inhibitors and AT1-receptor blockers have a superb track record in experimental animal models and in a host of clinical studies. Selective and nonselective blockers of the ET-1 receptors are important research tools and are also undergoing clinical trials. Inhibitors of the endothelin-converting enzyme have been developed. The recent elucidation of the endothelin-converting enzyme's physical structure should facilitate the development of still more novel compounds to inhibit ET-1 generation. We have recently engendered supportive evidence in this regard.
authors.affiliation: HELIOS Klinikum-Berlin, Medical Faculty of the Charitè, Humboldt University of Berlin, Germany.
authors.forename: D N
authors.initials: DN
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Fiebeler
authors.forename: J K
authors.initials: JK
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Dechend
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D014657:Vasculitis / Q000503:physiopathology*
chemical_list: D019332:Endothelin-1; D016328:NF-kappa B; D000804:Angiotensin II