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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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Effects of OLM treatment on induced CRF rats and comparisons among different groups (n = 14 in each group). Z c, aortic characteristic impedance (A); Cm, systemic arterial compliance (B); Rf , wave reflection factor (C); τ, wave transit time (D); NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.
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Figure 2: Effects of OLM treatment on induced CRF rats and comparisons among different groups (n = 14 in each group). Z c, aortic characteristic impedance (A); Cm, systemic arterial compliance (B); Rf , wave reflection factor (C); τ, wave transit time (D); NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.

Mentions: Figure 2 depicts the aortic characteristic impedance [32] and wave reflection factor (Rf) from the CRF rats were significantly increased than that from the controls (0.54 ± 0.03 vs. 0.76 ± 0.03 mmHg sec/ mL, p < 0.05) (Figure 2A, C). These changes were accompanied by the decreases of aortic compliance (Cm) (13.50 ± 0.60 vs. 5.03 ± 0.46, p < 0.05, Figure 2C) and wave transit time (τ) (27.62 ± 1.02 vs. 16.26 ± 0.59 ms, p < 0.05, Figure 2D). Treatment with OLM showed significant effects on retarding the CRF-induced mechanical alterations in the Windkessel vessels (Table 1), as manifested by the 39% reduction in aortic characteristic impedance (Zc, 2.23 ± 0.21 vs. 1.36 ± 0.08, p < 0.05) and the 75.3% increase in aortic compliance (Cm, 5.03 ± 0.46 vs. 8.82 ± 0.92, p <0.05). Early return with the augmented magnitude of the reflected wave from the peripheral circulation in CRF rats was impeded following OLM treatment, as demonstrated by the increase of 50.3% in wave transit time (τ, 16.26 ± 0.59 vs. 24.44 ± 1.76, 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)

Effects of OLM treatment on induced CRF rats and comparisons among different groups (n = 14 in each group). Z c, aortic characteristic impedance (A); Cm, systemic arterial compliance (B); Rf , wave reflection factor (C); τ, wave transit time (D); 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 2: Effects of OLM treatment on induced CRF rats and comparisons among different groups (n = 14 in each group). Z c, aortic characteristic impedance (A); Cm, systemic arterial compliance (B); Rf , wave reflection factor (C); τ, wave transit time (D); NC, normal controls; CRF, chronic renal failure; OLM, olmesartan.
Mentions: Figure 2 depicts the aortic characteristic impedance [32] and wave reflection factor (Rf) from the CRF rats were significantly increased than that from the controls (0.54 ± 0.03 vs. 0.76 ± 0.03 mmHg sec/ mL, p < 0.05) (Figure 2A, C). These changes were accompanied by the decreases of aortic compliance (Cm) (13.50 ± 0.60 vs. 5.03 ± 0.46, p < 0.05, Figure 2C) and wave transit time (τ) (27.62 ± 1.02 vs. 16.26 ± 0.59 ms, p < 0.05, Figure 2D). Treatment with OLM showed significant effects on retarding the CRF-induced mechanical alterations in the Windkessel vessels (Table 1), as manifested by the 39% reduction in aortic characteristic impedance (Zc, 2.23 ± 0.21 vs. 1.36 ± 0.08, p < 0.05) and the 75.3% increase in aortic compliance (Cm, 5.03 ± 0.46 vs. 8.82 ± 0.92, p <0.05). Early return with the augmented magnitude of the reflected wave from the peripheral circulation in CRF rats was impeded following OLM treatment, as demonstrated by the increase of 50.3% in wave transit time (τ, 16.26 ± 0.59 vs. 24.44 ± 1.76, 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