CLINICAL RESEARCH
Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients
Kwang Kon Koh, MD, FACC*,*,
Jeong Yeal Ahn, MD ,
Seung Hwan Han, MD*,
Dae Sung Kim, MD ,
Dong Kyu Jin, MD*,
Hyung Sik Kim, MD ,
Mi-Seung Shin, MD*,
Tae Hoon Ahn, MD*,
In Suck Choi, MD* and
Eak Kyun Shin, MD*
* Departments of Cardiology, Gachon Medical School, Incheon, South Korea
Clinical Pathology, Gachon Medical School, Incheon, South Korea
Radiology, Gachon Medical School, Incheon, South Korea
Preventive Medicine (Biostatistics), Gachon Medical School, Incheon, South Korea
Manuscript received November 7, 2002;
accepted December 6, 2002.
* Reprint requests and correspondence: Dr. Kwang Kon Koh, Vascular Medicine and Atherosclerosis Unit, Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, South Korea 405-760.
kwangk{at}ghil.com
OBJECTIVES: 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 µM (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  r 0.195) and between these changes and reduction of diastolic BP (–0.262 r 0.197). There were no significant correlations between markers of inflammation and flow-mediated dilation percent or reduction of oxidant stress (–0.119 r 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.
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Abbreviations and Acronyms
| | AII | = angiotensin II | | AT1 | = angiotensin II type 1 | | BP | = blood pressure | | CRP | = C-reactive protein | | LDL | = low-density lipoprotein | | MCP | = monocyte chemoattractant protein | | MDA | = malondialdehyde | | MMP | = matrix metalloproteinase protein | NF B | = nuclear transcription factor | | NO | = nitric oxide | | PAI-1 | = plasminogen activator inhibitor type-1 | | TNF | = tumor necrosis factor |
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