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Effects of olmesartan on arterial stiffness in rats with chronic renal failure.

Chuang YC, Wu MS, Su YK, Fang KM - Cardiovasc Diabetol (2012)

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Physiology, College of Medicine, National Taiwan University, Taipei City, Taiwan. d93441002@ntu.edu.tw

ABSTRACT

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.

Conclusion: 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.

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Representative Western blot and the corresponding level of advanced glycation end products (AGEs) in the aortas of rats (n = 5) analyzed by densitometry. Lane 1: NC; lane 2: CRF; lane 3: CRF + OLM. All data were normalized to the NC. NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.
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Figure 4: Representative Western blot and the corresponding level of advanced glycation end products (AGEs) in the aortas of rats (n = 5) analyzed by densitometry. Lane 1: NC; lane 2: CRF; lane 3: CRF + OLM. All data were normalized to the NC. NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.

Mentions: The immunointensity indicating AGE accumulation was higher in the media aortic wall of CRF rats (Figure 3), which was significantly reduced following OLM treatment for 8 weeks. Consequently, the amount of AGEs was 142% increased in collagen samples from CRF rats compared with control samples, displaying a molecular weight fragments between 26 and 34 KDa (Figure 4). After treatment with OLM for 8 weeks, AGEs decreased by 32% in glycation-derived modification of aortic collagen (p < 0.05).


Effects of olmesartan on arterial stiffness in rats with chronic renal failure.

Chuang YC, Wu MS, Su YK, Fang KM - Cardiovasc Diabetol (2012)

Representative Western blot and the corresponding level of advanced glycation end products (AGEs) in the aortas of rats (n = 5) analyzed by densitometry. Lane 1: NC; lane 2: CRF; lane 3: CRF + OLM. All data were normalized to the NC. NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472279&req=5

Figure 4: Representative Western blot and the corresponding level of advanced glycation end products (AGEs) in the aortas of rats (n = 5) analyzed by densitometry. Lane 1: NC; lane 2: CRF; lane 3: CRF + OLM. All data were normalized to the NC. NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.
Mentions: The immunointensity indicating AGE accumulation was higher in the media aortic wall of CRF rats (Figure 3), which was significantly reduced following OLM treatment for 8 weeks. Consequently, the amount of AGEs was 142% increased in collagen samples from CRF rats compared with control samples, displaying a molecular weight fragments between 26 and 34 KDa (Figure 4). After treatment with OLM for 8 weeks, AGEs decreased by 32% in glycation-derived modification of aortic collagen (p < 0.05).

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Physiology, College of Medicine, National Taiwan University, Taipei City, Taiwan. d93441002@ntu.edu.tw

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus