[Tissue consequence of renin-angiotensin system activation].
The renin-angiotensin system (RAS) is compartmented between the circulating blood and pericellular spaces. Whereas renin and its substrate diffuse easily from one compartment to another, angiotensin peptides act in the compartment where there are generated. Renin is trapped in tissues by low- and high-affinity receptors. In target cells, angiotensin II/AT1 receptor interaction generates various signals, including an immediate functional calcium-dependent response, secondary hypertrophy, and a late proinflammatory and procoagulant response. These late pathological effects are mediated by NADPH oxidase-generated oxygen free radicals and NF-k-B activation. In vivo, renin tissue binding and converting-enzyme induction are the main determinants of RAS involvement in vascular remodeling. The main target cells of interstitial angiotensin II are vascular smooth muscle cells and fibroblasts, whereas endothelial cells and circulating leukocytes are the main targets of circulating angiotensin II. In vivo, angiotensin II participates in the vascular wall hypertrophy associated with hypertension. In diabetes, as in other localized fibrotic cardiovascular diseases, the tissular effects of angiotensin II are mainly dependent on its ability to induce TGF-beta expression. In experimental atherosclerosis, angiotensin II infusion induces aneurysm formation mediated by activation of circulating leucocytes. Angiotensin II antagonist therapy has beneficial effects on pathological remodeling in animal models, but it remains to be determined whether this is also the case in humans.
Michel
Jean-Baptiste
JB
Inserm U460, CHU Xavier Bichat, 75018 Paris. jbmichel@bichat.inserm.fr
D000804:Angiotensin II / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000503:physiopathology; D001777:Blood Coagulation / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007249:Inflammation; D011956:Receptors, Cell Surface / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction; D025262:Vacuolar Proton-Translocating ATPases / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D000093342:Prorenin Receptor
D000804:Angiotensin II; D002118:Calcium; D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; D014662:Vasoconstrictor Agents; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor