Abstract
BackgroundIt has been suggested that the antioxidant properties of olmesartan (OLM), an angiotensin II type 1 receptor (AT1R) 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).MethodsCRF 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.ResultsAll 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.ConclusionOLM 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.
Highlights
It has been suggested that the antioxidant properties of olmesartan (OLM), an angiotensin II type 1 receptor (AT1R) blocker, contribute to renal protection rather than blood pressure lowering effects despite the fact that causal relationships between hypertension and renal artery disease exist
Apart from significantly lowering blood pressure, all the above abnormalities in chronic renal failure (CRF) rats were effectively ameliorated after 8 weeks of OLM treatment (Table 1)
In comparison with normal controls, CRF rats showed significantly affected hemodynamics characterized by decreased heart rate (396.26 ± 10.76 vs. 364.30 ± 10.02 beats/min, p
Summary
It has been suggested that the antioxidant properties of olmesartan (OLM), an angiotensin II type 1 receptor (AT1R) blocker, contribute to renal protection rather than blood pressure lowering effects despite the fact that causal relationships between hypertension and renal artery disease exist. The accumulation of advanced glycation end products (AGEs) due to reduced capability of detoxification and excretion in CKD patients has been confirmed to worsen vascularpathy [3,4]. AGEs stiffen collagen backbones [5], promote collagen deposition in heart and aorta [6], increase the expression of growth factors and cytokines [7] and induce inflammation [8]. These products can lead to glomerular and tubulointerstitial injury. ARBs reduced AGE formation by blocking excess oxidative stress has been verified in vitro [7]; the protective effect of ARBs on AGE formation remained controversial in clinical study [15]
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