Beneficial Effect of T-Type Calcium Channel Blockers on Endothelial Function in Patients with Essential Hypertension

Oshima, Tetsuya; Ozono, Ryoji; Yano, Yumihiko; Higashi, Yukihito; Teragawa, Hiroki; Miho, Narimasa; Ishida, Takafumi; Ishida, Mari; Yoshizumi, Masao; Kambe, Masayuki

doi:10.1291/hypres.28.889

Cited by 57 publications

(45 citation statements)

References 30 publications

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“…6 However, it is still controversial whether improvement of endothelial function is an effect of the RAS inhibitor class because several investigators were unable to observe such an effect for ARB 7 in spite of beneficial effects seen for other classes of antihypertensives. 8 Basic research has clearly demonstrated that the Ang II-mediated signal transduction pathway induces inflammation and oxidative stress. 9,10 In the clinical setting, ACEI and ARB reportedly improve endothelial function by increasing endothelium-bound (released by heparin injection) extracellular superoxide dismutase (EC-SOD) activity, 6 supporting the above observations.…”

Section: Introductionmentioning

confidence: 99%

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

et al. 2011

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Endothelial dysfunction in essential hypertension is an independent predictor for future cardiovascular events. Although inhibition of the renin-angiotensin system (RAS) reportedly improves endothelial function through its effects on oxidative stress and inflammation, questions remain regarding the factors that are pivotal for improvement of endothelial function by RAS inhibition. We therefore performed a prospective, randomized crossover trial in which an angiotensin II type 1 receptor antagonist, olmesartan and calcium channel blocker, amlodipine, were compared in 31 essential hypertensive patients. Results showed that, although both treatments achieved comparable lowering of blood pressure (BP), olmesartan, but not amlodipine, significantly improved endothelial function as evaluated by flow-mediated vasodilation (FMD) in the brachial artery. Although no significant changes in diabetic and lipid parameters were observed with either drug, olmesartan slightly decreased estimated glomerular filtration rate, which, surprisingly, translated into decreased microalbuminuria. In a similar vein, olmesartan reduced serum C-reactive protein and increased urine antioxidant levels compared with baseline, and reduced urine 8-epi-prostaglandin F2a levels compared with both baseline and amlodipine. Finally, although overall changes in plasma extracellular superoxide dismutase (EC-SOD) levels were not modulated by either treatment, for olmesartan there was a positive correlation between changes in FMD and those in EC-SOD levels. In conclusion, olmesartan improved endothelial function in hypertensive patients independent of its BP-lowering effect, which was due, at least in part, to its antioxidative property. Therefore, olmesartan might provide a greater long-term benefit for hypertensive patients with impaired endothelial function than amlodipine.

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Section: Introductionmentioning

confidence: 99%

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

et al. 2011

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“…Efonidipine improves endothelial function in patients with hypertension when compared with doses of nifedipine that result in comparable decreases in mean blood pressure (9). Therefore, we hypothesized that efonidipine therapy may simultaneously improve endothelial dysfunction, adipocytokine profiles, and other metabolic parameters in nondiabetic patients with hypertension.…”

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confidence: 99%

Efonidipine Simultaneously Improves Blood Pressure, Endothelial Function, and Metabolic Parameters in Nondiabetic Patients With Hypertension

et al. 2007

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Hypertension is characterized by endothelial dysfunction and frequently clusters with metabolic disorders that are characterized by insulin resistance (1,2). These comorbidities may be explained, in part, by reciprocal relationships between endothelial dysfunction and insulin resistance (1). By contrast with calcium channel blockers (CCBs), treatment of hypertension with ␤-blockers and diuretics is associated with a higher risk of type 2 diabetes (3). This advantage of CCBs may relate to specific mechanisms that target the vicious synergy between endothelial dysfunction and insulin resistance. CCBs activate nitric oxide (NO) synthase in vitro and enhance NO production in vivo (4). This may impact on the roles of adiponectin, leptin, and resistin to influence metabolic signals, inflammation, and atherosclerosis (5-7).Efonidipine hydrochloride is a 1,4-dihydropyridine-type CCB with longlasting vasodilator actions and little reflex tachycardia (8). Efonidipine improves endothelial function in patients with hypertension when compared with doses of nifedipine that result in comparable decreases in mean blood pressure (9). Therefore, we hypothesized that efonidipine therapy may simultaneously improve endothelial dysfunction, adipocytokine profiles, and other metabolic parameters in nondiabetic patients with hypertension. RESEARCH DESIGN ANDMETHODS -We evaluated effects of efonidipine in a randomized, doubleblind, placebo-controlled, crossover study. Thirty-nine hypertensive patients (systolic blood pressure [SBP] Ͻ180 mmHg and diastolic blood pressure [DBP] Ͻ110 mmHg) were considered eligible for this study. We excluded patients with severe hypertension, unstable angina, acute myocardial infarction, or renal insufficiency. None of our subjects were diabetic (based on history or criteria according to the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [10]) or smokers. To minimize acute side effects, during an initial run-in period, study medication was titrated from 40 to 80 mg efonidipine upwards over a 2-week period if no hypot e n s i o n ( S B P Ͻ 1 0 0 m m H g ) o r hypertension (SBP Ͼ140 mmHg) was noted. After the run-in period, all patients underwent a 3-week washout period. At the end of the washout period, participants were randomly assigned to either 40 -80 mg efonidipine or placebo daily during 8 weeks. Patients were then crossed over to the second treatment arm on completion of the first treatment arm (without washout phase). The Green Cross Pharmaceutical company (Yongin, Korea) provided the identical placebo (purchased by investigators). One patient suffered from facial flushing and was withdrawn. Thus, data from 38 patients were analyzed. This study was approved by the Gil Hospital Institute Review Board.Blood samples were obtained at 8:00 A.M. following an overnight fast before and after each treatment period. Assays for plasma insulin, malondialdehyde, adiponectin, leptin, and resistin were performed in duplicate by immunoradiometric assay or by enzymel i n k e ...

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“…28,29 In addition, some interventions, including treatment with antihypertensive agents, statins, supplementation therapy, treatment with antioxidants vitamins, and lifestyle modification, have been shown to improve endothelial function and prevent cardiovascular complications. [20][21][22]30,31 Therefore, from a clinical perspective, it is important to estimate the basal condition of endothelial function and of the improvement in endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Measurement of Flow-Mediated Vasodilation of the Brachial Artery A Comparison of Measurements in the Seated and Supine Positions

Soga

Nishioka

Nakamura

et al. 2007

Circ J

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Study ProtocolAll studies were performed in the morning, after overnight fasting, in a quiet, dark, air-conditioned room (conCirc J 2007; 71: 736 -740 (Received September 11, 2006; revised manuscript received February 13, 2007; accepted February 16, 2007 Background Measurement of flow-mediated vasodilation (FMD) is used to assess endothelial function in humans and according to the guidelines, subjects must remain supine during the study. However, measurement of FMD while seated would be more comfortable and convenient for patients, so the purpose of this study was to determine the effect of the patient's position on FMD results. Methods and ResultsHigh-resolution ultrasonography, a linear array transducer (13 MHz) and an arm -holding device were used to measure arterial diameter in response to reactive hyperemia (FMD, cuff inflated to 50 mmHg above systolic blood pressure for 5 min) and in response to sublingual nitroglycerine (NTG, 75 g) in 31 subjects, which included those with cardiovascular diseases. There was no significant difference between basal or peak hyperemic blood flow in the seated or supine position. Basal brachial artery diameter, FMD and vascular response to NTG were similar in both positions (basal diameter: 3.8±0.4 vs 3.9±0.4 mm, FMD: 7.3±4.3% vs 7.2±4.5%, NTG: 13.1±5.1% vs 12.8±5.6%). Conclusions The findings suggest that measurement of FMD in the seated position is as useful as measuring it in the supine position for assessing endothelial function. This flexibility of position is better for patients and physicians, and should lead to more widespread measurement of FMD. (Circ J 2007; 71: 736 -740)

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Beneficial Effect of T-Type Calcium Channel Blockers on Endothelial Function in Patients with Essential Hypertension

Abstract: Endothelial function is impaired in essential hypertension. T-type but not L-type voltage-gated Ca

Cited by 57 publications

References 30 publications

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

Efonidipine Simultaneously Improves Blood Pressure, Endothelial Function, and Metabolic Parameters in Nondiabetic Patients With Hypertension

Measurement of Flow-Mediated Vasodilation of the Brachial Artery A Comparison of Measurements in the Seated and Supine Positions

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