Emerging role of angiotensin II type 1 receptor blockers for the treatment of endothelial dysfunction and vascular inflammation.
BACKGROUND
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.


OBJECTIVE
To review current evidence regarding the effects of AT1RBs on endothelial dysfunction in patients.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mancini
G B John
GB
Vancouver Hospital and Health Sciences Centre, University of British Columbia, Canada. mancini@interchange.ubc.ca
D000179:Acrylates / Q000008:administration & dosage; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D015415:Biomarkers / Q000032:analysis; D001713:Biphenyl Compounds / Q000008:administration & dosage; D003324:Coronary Artery Disease / Q000188:drug therapy; D003627:Data Interpretation, Statistical; D003920:Diabetes Mellitus / Q000188:drug therapy; D019040:E-Selectin / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage; D000077405:Irbesartan; D019808:Losartan / Q000008:administration & dosage; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles / Q000008:administration & dosage; D013876:Thiophenes; D014657:Vasculitis / Q000188:drug therapy*
D000179:Acrylates; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D019040:E-Selectin; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D013876:Thiophenes; C068373:eprosartan; D000077405:Irbesartan; D019808:Losartan; C081643:candesartan