title: From tissue angiotensin converting enzyme inhibition to antihypertensive effect.
abstract: The renin-angiotensin system (RAS) has long been regarded as a classical hormonal system, with angiotensin II (ANG II) being the circulating effector peptide. In recent years, evidence for additional RAS in various organs, including vascular wall, kidney, adrenal gland, heart, and brain, has been obtained. Drugs interfering with the RAS such as the converting enzyme (CE) inhibitors may, therefore, not only inhibit the plasma RAS but also inhibit these tissue RAS. Such a "tissue" RAS inhibition has been repeatedly demonstrated in animal experiments, and in some cases it correlated better with the cardiovascular actions of the CE inhibitors than did inhibition of plasma RAS. In the vascular wall, a local inhibition of ANG II synthesis may contribute not only to the reduction of vascular tone but also to the marked regression of media hypertrophy seen after CE inhibitor treatment. Vascular ANG II generation by CE appears to occur almost exclusively at the luminal surface of the endothelium. Locally formed ANG II may then contribute to the pool of circulating ANG II (endocrine ANG II) or feed back to adjacent cells without being transported by the blood (paracrine ANG II). Thus, CE inhibitors may not have to penetrate into deeper layers of the vascular wall to inhibit the vascular RAS, but may rather prevent the paracrine actions of locally generated ANG II.
authors.affiliation: Department of Pharmacology, University of Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Veltmar
authors.forename: P
authors.initials: P
authors.lastname: Gohlke
authors.forename: T
authors.initials: T
authors.lastname: Unger
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004702:Endocrine Glands / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006984:Hypertrophy; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents