title: Vascular renin-angiotensin-system, endothelial function and atherosclerosis?
abstract: Clinical observations demonstrate an enhanced risk for myocardial infarction in patients with sustained activation of the local and/or systemic renin-angiotensin system, such as a high renin-sodium profile or a heritably enhanced expression of angiotensin converting enzyme. Chronic renin-angiotensin system blockade by angiotensin converting enzyme inhibition in patients with moderate heart failure reduces the rate of myocardial infarction and reinfarction. Preliminary experimental evidence suggests that these clinical observations may be partially explained by a proatherogenic effect of an activated renin-angiotensin system, which can downregulate the endothelial releasability of nitric oxide. Nitric oxide exerts many potentially antiatherogenic effects on endothelium, platelets and low density lipoproteins and indirectly on monocytes and leukocytes. Hypertension-induced chronic distension of elastic arteries upregulates the local renin-angiotensin system in these arteries and thereby downregulates nitric oxide releasability. Enhanced local synthesis of the trophic factor angiotensin-II and reduced releasability of the antitrophic factor nitric oxide appear to cooperate in the trophic adaptation of the distended vessel wall to the enhanced load, but with the disadvantage of enhanced susceptibility for atheroma development due to reduced releasability of nitric oxide. Chronic blockade of the renin angiotensin system by angiotensin converting enzyme inhibitors or by angiotensin receptor type-1 antagonists normalizes a reduced endothelial releasability of nitric oxide in several models, partially by a bradykinin-dependent mechanism. This endothelial protection proved to attenuate the progression of atherosclerosis in experimental models. The antiatherogenic potential of renin angiotensin system blockade in humans is presently under study.
authors.affiliation: Institut für Pathophysiologie Martin-Luther-Universität Halle-Wittenberg.
authors.forename: J
authors.initials: J
authors.lastname: Holtz
authors.forename: R M
authors.initials: RM
authors.lastname: Goetz
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide