Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients.
OBJECTIVE
We investigated the vascular effects of candesartan in hypertensive patients.


BACKGROUND
The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The plausible mechanisms are that angiotensin II promotes superoxide anion generation, endothelial dysfunction, inflammation, and impaired fibrinolysis. The effects of candesartan on these conditions have not been clearly observed.


METHODS
We administered placebo or candesartan 16 mg daily during two months to 45 patients with mild-to-moderate hypertension. This was a randomized, double-blind, placebo-controlled, crossover study in design.


RESULTS
Candesartan did not significantly change lipoprotein levels. However, compared with placebo, candesartan significantly reduced plasma levels of malondialdehyde from 1.50 +/- 0.07 to 1.29 +/- 0.09 microM (p = 0.009); improved the percent flow-mediated dilator response to hyperemia from 5.17 +/- 0.24 to 6.22 +/- 0.26% (p < 0.001); and, furthermore, reduced plasma levels of monocyte chemoattractant protein (MCP-1) from 213 +/- 8 to 190 +/- 7 pg/ml (p = 0.003), tumor necrosis factor-alpha from 2.93 to 2.22 pg/ml (p = 0.026), and plasminogen activator inhibitor type 1 from 74 +/- 4 to 53 +/- 4 ng/ml (p < 0.001) but not C-reactive protein (CRP), matrix metalloproteinase protein, and fibrinogen. There were no significant correlations between these changes and reduction of systolic blood pressure (BP) (-0.247 < or = r < or = 0.195) and between these changes and reduction of diastolic BP (-0.262 < or = r < or = 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (-0.119 < or = r < or = 0.127). Furthermore, we observed no significant correlations between CRP and MCP-1 levels (r = -0.162).


CONCLUSIONS
Inhibition of the angiotensin II type 1 (AT1) receptor in hypertensive patients reverses endothelial dysfunction, measured as an improvement in flow-mediated dilation and fibrinolysis and reduction of oxidant stress and inflammatory cytokines, suggesting that AT1 receptor blocker therapy has antiatherogenic effects.
Koh
Kwang Kon
KK
Department of Cardiology, Vascular Medicine and Atherosclerosis Unit, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea 405-760. kwangk@ghil.com
Ahn
Jeong Yeal
JY
Han
Seung Hwan
SH
Kim
Dae Sung
DS
Jin
Dong Kyu
DK
Kim
Hyung Sik
HS
Shin
Mi-Seung
MS
Ahn
Tae Hoon
TH
Choi
In Suck
IS
Shin
Eak Kyun
EK
D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins / Q000187:drug effects / Q000502:physiology; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D018932:Chemokine CCL2 / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014666:Vasomotor System / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018932:Chemokine CCL2; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D013777:Tetrazoles; D008315:Malondialdehyde; C081643:candesartan