Vascular and metabolic effects of candesartan: insights from therapeutic interventions.
BACKGROUND
Effects of angiotensin II type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus formation. Hypertensive patients have impaired endothelial functions that have positive predictive power with respect to future cardiovascular events.


OBJECTIVE
The present review will focus on multiple mechanisms underlying vascular and metabolic effects of ARBs that may synergize to prevent or regress atherosclerosis, onset of diabetes, and coronary heart disease.


CONCLUSIONS
Angiotensin II accelerates the development of atherosclerosis by activating angiotensin II type 1 receptors that then promote superoxide anion generation and oxidative stress, leading to activation of nuclear transcription factor and endothelial dysfunction. Activation of angiotensin II type 1 receptors also stimulates increased expression of plasminogen activator inhibitor type 1 and tissue factor. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated production of nitric oxide from the endothelium and decreased blood flow to skeletal muscle. Increasing insulin sensitivity therefore improves endothelial function, and this may be an additional mechanism whereby ARBs decrease the incidence of coronary heart disease and the onset of diabetes. Adiponectin serves to link obesity with insulin resistance. In addition, adiponectin has anti-atherogenic properties.
Koh
Kwang Kon
KK
Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea. kwangk@gilhospital.com
Quon
Michael J
MJ
Han
Seung Hwan
SH
Chung
Wook-Jin
WJ
Kim
Jeong-A
JA
Shin
Eak Kyun
EK
D052242:Adiponectin / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D009569:Nitric Oxide; D002097:C-Reactive Protein; C081643:candesartan