eprosartan and Vasculitis

Angiotensin II type 1 receptor blockers (AT1RBs) share the effect of attenuating angiotensin II actions with angiotensin-converting enzyme inhibitors (ACEIs) but differ in other respects. Notably, the impact of unopposed angiotensin type 2 receptor stimulation and the absence of augmentation of bradykinin through inhibition of the kininase pathway may lead to differences between the effects of AT1RBs and ACEIs. ACEIs have been shown to improve endothelial dysfunction in many clinical settings.. To review current evidence regarding the effects of AT1RBs on endothelial dysfunction in patients.. MEDLINE and Current Contents searches, augmented by careful analyses of the bibliographies in the identified papers, were used to identify studies assessing the effects of chronic, oral use of AT1RBs on endothelial function and related inflammatory markers in patients. Animal studies and human studies using single doses or intravenous infusions were excluded.. Clinical studies are available pertaining to the elderly and patients with coronary artery disease, hypertension and diabetes. The effect on endothelial dysfunction induced by postprandial lipemia has also been assessed. In general, AT1RBs improve vasomotor endothelial dysfunction and some inflammatory markers, but a few studies comparing ACEIs directly with AT1RBs suggest that AT1RBs may be inferior. AT1RB activity on endothelial dysfunction in patients with type I diabetes has not been shown.. AT1RBs are an important addition to the therapy of endothelial dysfunction and vascular inflammation in patients. Further research is necessary to determine which AT1RBs and which dosing regimens are optimal.

Topics: Acrylates; Aged; Antihypertensive Agents; Benzimidazoles; Biomarkers; Biphenyl Compounds; Coronary Artery Disease; Data Interpretation, Statistical; Diabetes Mellitus; E-Selectin; Endothelium, Vascular; Humans; Hypertension; Imidazoles; Irbesartan; Losartan; Receptor, Angiotensin, Type 1; Receptors, Angiotensin; Tetrazoles; Thiophenes; Vasculitis

The purpose of this investigation was to determine whether angiotensin II receptor (AII1R) antagonism interferes with cardiac monocyte chemoattractant protein-1 (MCP-1) expression in hypertrophic cardiomyopathy and failure.. We studied the effects of the AII1R antagonist eprosartan on MCP-1 expression, and on the recruitment of macrophages into the myocardium in a model of cardiac hypertrophy and morbidity/mortality.. Stroke-prone spontaneously hypertensive rats fed a high-salt, high-fat diet (SFD) developed heart failure characterized by left ventricular (LV) hypertrophy/pathology and hypocontractility. These rats received either normal diet, SFD, or SFD with the daily administration of 30 mg/kg eprosartan for 28 weeks. LV function and wall thickness was assessed by echocardiography, MCP-1 expression was measured by TaqMan real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry, and macrophage infiltration into the LV was determined by microscopy.. Eprosartan reduced the rate of morbidity/mortality (P = 0.001), LV MCP-1 mRNA (P < 0.05) and protein expression (P < 0.01), and LV macrophage infiltration (P < 0.01), while preserving ventricular function (P < 0.05). Eprosartan also produced a moderate (16%; P < 0.05) decrease in blood pressure.. These data demonstrate that AII1R antagonism in an animal model of hypertensive heart disease reduces MCP-1 expression in the myocardium that results in reduced macrophage recruitment. These effects parallel the preservation of LV systolic function and the reduction in cardiac remodeling/disease progression and reduced morbidity/mortality. Suppression of MCP-1 expression might explain in part the beneficial effects of AII1R antagonism in this model.

Topics: Acrylates; Angiotensin II; Animals; Antihypertensive Agents; Chemokine CCL2; Down-Regulation; Hypertension; Hypertrophy, Left Ventricular; Imidazoles; Immunohistochemistry; Macrophages; Myocardial Contraction; Myocardium; Rats; Rats, Inbred SHR; RNA, Messenger; Thiophenes; Ultrasonography; Vasculitis