In Vitro Antioxidant Activity of Calcium Antagonists against LDL Oxidation Compared with α-Tocopherol

Lupo, E.; Locher, Rudolf; Weisser, Burkhard; Vetter, W

doi:10.1006/bbrc.1994.2396

Cited by 79 publications

(38 citation statements)

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“…It is well documented in several experimental models that calcium antagonists, including lercanidipine, show antioxidant properties. 39,40 In agreement with this possibility and with previous evidence in humans, 21 in the current study lercanidipine treatment not only prevented the…”

Section: Discussionsupporting

confidence: 93%

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

et al. 2003

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Abstract-Essential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxidative stress-induced nitric oxide (NO) breakdown and compensatory production of a hyperpolarizing factor. To test whether calcium antagonist treatment can restore NO availability and prevent hyperpolarization through antioxidant properties, in 15 healthy subjects and 15 patients with essential hypertension, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial bradykinin (5, 15, 50 ng/100 mL per minute), an endothelium-dependent vasodilator, in basal conditions, during infusion of N G -monomethyl-L-arginine (L-NMMA, 100 g/100 mL per minute), an NO-synthase inhibitor, and ouabain (0.72 g/100 mL per minute), an Na ϩ -K ϩ ATPase inhibitor to prevent hyperpolarization. These infusions were repeated in the presence of the antioxidant vitamin C (8 mg/100 mL/min). The response to sodium nitroprusside was also evaluated. In controls, vasodilation to bradykinin was inhibited by L-NMMA and remained unchanged by ouabain or vitamin C. In hypertensive patients, vasodilation to bradykinin was blunted and resistant to L-NMMA but sensitive to ouabain. Vitamin C increased the response to bradykinin and restored the inhibiting effect of L-NMMA while preventing the effect of ouabain. In hypertensive patients, infusions were repeated after 3-month treatment with lercanidipine (10 to 20 mg daily). Lercanidipine decreased plasma lipoperoxides, isoprostanes, and malondialdehyde and increased plasma antioxidant capacity. Moreover, lercanidipine increased the vasodilation to bradykinin and restored the inhibiting effect of L-NMMA on bradykinin-induced vasodilation while preventing the effect of ouabain. Finally, vitamin C no longer exerted its facilitating activity. These results indicate that in essential hypertension, lercanidipine increases endothelium-dependent vasodilation by restoring NO availability and preventing hyperpolarization, an effect probably determined by antioxidant activity. Key Words: hypertension, essential Ⅲ endothelium Ⅲ nitric oxide Ⅲ endothelium-derived factors Ⅲ free radicals Ⅲ antioxidants Ⅲ calcium antagonists E ndothelium plays a primary role in the modulation of vascular tone 1 by producing and releasing relaxing substances including nitric oxide (NO) 2 and a not-yet identified hyperpolarizing factor (EDHF). 3 In the presence of several cardiovascular risk factors, endothelial cells can also produce contracting factors (EDCFs), which are mainly cyclooxygenase-dependent prostanoids (thromboxane A2 and prostaglandin H2) 4,5 or superoxide anions. 6 Essential hypertension is characterized by impaired endothelium-dependent vasodilation to specific agonists 7-9 as the result of a reduction in NO oxide availability 10,11 caused by production of oxidative stress. 12 In the presence of impaired NO availability, endothelium-dependent relaxation seems to be sustained by hyperpolarization, which probably acts as a compensatory mechanism. 13 Since endothelial dysfunct...

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Section: Discussionsupporting

confidence: 93%

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

et al. 2003

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“…This suggests that CR nifedipine may have a beneficial effect on the vascular system beyond its antihypertensive effect. 25,26,[34][35][36] In patients with essential hypertension, platelets appear to be preactivated or hyper-responsive to vasoactive agents. 37 In addition, the activation of platelets contributes to vascular structural changes and the development of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

et al. 2006

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Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.

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“…24 However, even though moxonidine could lower serum concentrations of catecholamines and renin, [25][26][27] no significant change in the susceptibility of LDL subclasses to copper-induced oxidative modification was found. Similarly, atenolol, which can also reduce plasma renin activity had no effect on the oxidation resistance of LDL, [28][29][30] while nifedipine and other calcium channel blockers displayed a significant dose-dependent capacity to protect LDL during copper-induced oxidation, 28,31 suggesting that calcium antagonists may potentially exert antiatherosclerotic properties via a reduction of the oxidative modification of LDL.…”

Section: Discussionmentioning

confidence: 99%

The effect of moxonidine on plasma lipid profile and on LDL subclass distribution

et al. 1999

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Moxonidine is a new antihypertensive agent whose mechanism of action appears to involve specific stimulation of imidazoline receptors resulting in an inhibition of the activity of the central and peripheral sympathetic nervous system. The drug seems to behave neutrally with respect to plasma lipid parameters. However, there are no data on the effects of moxonidine on the lowdensity lipoprotein (LDL) subclass pattern or on the LDL oxidation susceptibility, both of which are known to play a prominent role in the pathogenesis of atherosclerosis. Thus, we undertook the present study to examine the influence of moxonidine on the LDL subspecies profile and their susceptibility to copper-induced oxidative modification in 20 hypertensive patients (11 men, 9 women) aged 38-61 years. Moxonidine administered at a dose of 0.4 mg daily for 8 weeks produced a signifi-

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In Vitro Antioxidant Activity of Calcium Antagonists against LDL Oxidation Compared with α-Tocopherol

Cited by 79 publications

References 0 publications

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

Calcium Antagonist Treatment by Lercanidipine Prevents Hyperpolarization in Essential Hypertension

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

The effect of moxonidine on plasma lipid profile and on LDL subclass distribution

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