Effects of olmesartan on arterial stiffness in rats with chronic renal failure.
BACKGROUND
It has been suggested that the antioxidant properties of olmesartan (OLM), an angiotensin II type 1 receptor (AT(1)R) blocker, contribute to renal protection rather than blood pressure lowering effects despite the fact that causal relationships between hypertension and renal artery disease exist. This study aimed to examine the hypothesis whether the antioxidative activities of OLM were correlated to arterial stiffness, reactive oxygen species and advanced glycation end products (AGEs) formation in rats with chronic renal failure (CRF).


METHODS
CRF rats were induced by 5/6 nephrectomy and randomly assigned to an OLM (10 mg/day) group or a control group. Hemodynamic states, oxidative stress, renal function and AGEs were measured after 8 weeks of OLM treatment.


RESULTS
All the hemodynamic derangements associated with renal and cardiovascular dysfunctions were abrogated in CRF rats receiving OLM. Decreased cardiac output was normalized compared to control (p <0.05). Mean aortic pressure, total peripheral resistance and left ventricular weight/body weight ratio were reduced by 21.6% (p <0.05), 28.2% (p <0.05) and 27.2% ((p <0.05). OLM also showed beneficial effects on the oscillatory components of the ventricular after-load, including 39% reduction in aortic characteristic impedance (p < 0.05), 75.3% increase in aortic compliance (p <0.05) and 50.3% increase in wave transit time (p < 0.05). These results implied that OLM attenuated the increased systolic load of the left ventricle and prevented cardiac hypertrophy in CRF rats. Improved renal function was also reflected by increases in the clearances of BUN (28.7%) and serum creatinine (SCr, 38.8%). In addition to these functional improvements, OLM specifically reduced the levels of malondialdehyde (MDA) equivalents in aorta and serum by 14.3% and 25.1%, as well as the amount of AGEs in the aortic wall by 32% (p < 0.05) of CRF rats.


CONCLUSIONS
OLM treatment could ameliorate arterial stiffness in CRF rats with concomitant inhibition of MDA and AGEs levels through the reduction of oxidative stress in aortic wall.
Institute of Physiology, College of Medicine, National Taiwan University, Taipei City, Taiwan. d93441002@ntu.edu.tw
Yao-Chen
YC
Chuang
Ming-Shiou
MS
Wu
Yi-Kai
YK
Su
Kwang-Ming
KM
Fang
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D059289:Vascular Stiffness / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D008315:Malondialdehyde; C437965:olmesartan; D003404:Creatinine