Calcium Channel Blockades Exhibit Anti-Inflammatory and Antioxidative Effects by Augmentation of Endothelial Nitric Oxide Synthase and the Inhibition of Angiotensin Converting Enzyme in the NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Rat Aorta: Vasoprotective Effects beyond the Blood Pressure-Lowering Effects of Amlodipine and Manidipine

Toba, Hiroe; Nakagawa, Yoshitsugu; Miki, Shunsuke; Shimizu, Takahiro; Yoshimura, Akiko; Inoue, Riyako; Asayama, Jun; Kobara, Miyuki; Nakata, Tetsuo

doi:10.1291/hypres.28.689

Cited by 66 publications

(54 citation statements)

References 62 publications

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“…Surprisingly, in the present study, candesartan plus amlodipine combination therapy attenuated increased vascular ACE activity and its gene expression in SHR-SP, but neither candesartan monotherapy nor candesartan plus HCTZ combination therapy had the same effect. We did not confirm whether amlodipine monotherapy attenuated ACE activity in the SHR-SP in the present study; however, Toba et al 32 demonstrated that amlodipine, but not hydralazine, attenuated the increase of both vascular ACE activity and its gene expression in N o -nitro-L-arginine methyl ester-induced hypertensive rats, despite producing the same hypotensive effects as amlodipine and hydralazine. In N o -nitro-L-arginine methyl ester-induced hypertensive rats, Usui et al 33 reported that antioxidant drugs attenuated not only the increased oxidative stress, but also the induced vascular ACE activity.…”

Section: Discussioncontrasting

confidence: 92%

Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats

Jin

Shimosato²,

Saito

et al. 2010

Hypertens Res

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The vascular protective effects of placebo, candesartan (1 mg kg À1 per day) monotherapy, candesartan (1 mg kg À1 per day) and amlodipine (1 mg kg À1 per day) combination therapy, and candesartan (1 mg kg À1 per day) and hydrochlorothiazide (HCTZ) (10 mg kg À1 per day) combination therapy for 2 weeks were compared in stroke-prone, spontaneously hypertensive rats. Candesartan monotherapy significantly reduced blood pressure, and both combination therapies were equally and significantly lower than the monotherapy. Acetylcholine-induced vascular relaxation was significantly stronger in all therapeutic groups than in the placebo-treated group. Furthermore, the relaxation was significantly stronger in the candesartan plus amlodipine-treated group than in the candesartan-treated group; however, there was no significant difference between the candesartan-and candesartan plus HCTZ-treated groups. Vascular gene expressions of the NADPH oxidase subunits p22 phox , gp91 phox , NOX1 and NOX4 were significantly attenuated in all therapeutic groups compared with the placebo-treated group, and there were no significant differences among those groups. However, a significant augmentation of vascular superoxide dismutase activity was observed in the candesartan plus amlodipine-treated group, but not in other groups. Malondialdehyde levels in the vascular tissues were significantly attenuated in all therapeutic groups. Compared with the candesartan-treated group, significant attenuation was observed in the candesartan plus amlodipine-treated group, but not in the candesartan plus HCTZ-treated group. Immunohistological analysis showed that areas positive for 4-hydroxy-2-nonenal were significantly reduced in all therapeutic groups, but this reduction was significantly greater for the candesartan plus amlodipine-treated group than for the candesartantreated group. Thus, candesartan and amlodipine combination therapy could have a powerful protective effect in vascular tissues via the reduction of oxidative stress.

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Section: Discussioncontrasting

confidence: 92%

Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats

Jin

Shimosato²,

Saito

et al. 2010

Hypertens Res

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“…Amlodipine and manidipine are reported to possess the anti-inflammatory and antioxidant activity via the augmentation of eNOS expression and to have vasoprotective effects beyond the blood pressure-lowering effects (27). Taken together with our results, a Ca 2+ antagonist may potentially have preventive effects against cardiac remodeling after MI.…”

Section: Discussionsupporting

confidence: 78%

The Long-Acting Ca2+-Channel Blocker Azelnidipine Prevents Left Ventricular Remodeling After Myocardial Infarction

et al. 2007

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Abstract. Long-acting Ca 2+-channel blockers have been reported to be effective in treating ischemic heart disease. However, their effects on cardiac remodeling after myocardial infarction (MI) are still unclear. We performed this study to examine the effect of azelnidipine on left ventricular (LV) remodeling, including systolic and diastolic dysfunction, in rats with MI. MI was induced by ligation of the left anterior descending artery. The rats were then separated into 3 groups: a sham-operated group (n = 9), untreated MI group (n = 10), and azelnidipine-treated MI group (n = 10). Four weeks after MI, hemodynamic measurements and Doppler echocardiographic assessment were performed. LV weight and LV end-diastolic dimension were significantly higher in the untreated MI group than in the sham-operated group. Azelnidipine significantly prevented the increases in these parameters. Azelnidipine also improved the ejection fraction (42 ± 3%, P<0.05) and the E wave to A wave ratio (3.2 ± 0.5, P<0.05), compared with the untreated MI group (31 ± 3% and 5.3 ± 0.8, respectively). In conclusion, azelnidipine can prevent LV remodeling and improve systolic and diastolic function after MI. Administration of long-acting Ca 2+-channel blockers after MI is an effective strategy for treating MI.

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“…Hypertensive patients exhibit higher levels of plasma H 2 O 2 , increased plasma, and urine markers of oxidative stress such as TBARS, oxidized low-density lipoprotein (oxLDL), and 8 iso-prostane and reduced antioxidant capacity, compared with normotensive subjects (20,171,184,205,229). Isoprostanes are stereoisomers of prostaglandins, which are formed mainly by non-enzymatic peroxidation of arachidonic acid by ROS.…”

Section: Ros Oxidative Stress and Human Hypertensionmentioning

confidence: 99%

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

236

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

show abstract

Cited by 66 publications

References 62 publications

Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats

Candesartan and amlodipine combination therapy provides powerful vascular protection in stroke-prone spontaneously hypertensive rats

The Long-Acting Ca2+-Channel Blocker Azelnidipine Prevents Left Ventricular Remodeling After Myocardial Infarction

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

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