Dietary magnesium improves endothelial dependent relaxation of balloon injured arteries in rats

doi:10.1016/S0021-9150(98)00069-0

Atherosclerosis

Volume 139, Issue 2, 4 August 1998, Pages 237-242

https://doi.org/10.1016/S0021-9150(98)00069-0 Get rights and content

Abstract

The purpose of the present study was to examine the importance of magnesium in endothelial function after arterial balloon injury. Male Wistar rats were fed normal, high or low concentrations of magnesium. Three weeks later the animals underwent endothelial injury of the thoracic aorta by a balloon catheter or a sham operation. Biochemical, histological and endothelial function analysis were performed 15 days after the surgical treatment. The animals fed a low magnesium diet presented the lowest level of serum magnesium and the highest ionized blood calcium levels. Histomorphometric analysis revealed no differences among groups neither regarding the magnitude of intimal thickening nor the recovery of endothelial coverage. However, when vasoreactivity responses were compared in the balloon-injured group, those animals fed a high magnesium diet had the better endothelium-dependent vascular relaxation. In conclusion, a higher magnesium level in the diet was beneficial to vessels that underwent endothelial injury by balloon catheter.

Introduction

Magnesium deficiency has been reported in diabetes, hypertension, and coronary heart disease [1]. Following therapeutic procedures such as coronary angioplasty, endothelial cell dysfunction is common and correlated with endothelial injury [2]. Experimental studies have shown endothelial denudation immediately after angioplasty and impaired endothelial reactivity for several weeks even in the presence of a regenerated endothelial surface 3, 4.

It is widely recognized that calcium plays an important role in the formation of endothelium-derived relaxing and constrictor factors 5, 6, 7, 8. Since magnesium has been described as a calcium antagonist agent capable of displacing calcium of intracellular sites and blocking the voltage-dependent L- or T-type Ca²⁺ channels and receptor-mediated Ca²⁺ permeable non-selective cation currents in vascular smooth muscle cells [9], it can affect the vascular reactivity to a number of vasoconstrictors and also the endothelial-dependent vasorelaxation for some agonists [10]. Therefore, the goal of the present study was to verify the importance of dietary magnesium on endothelium-dependent vascular relaxation during the healing process after balloon-injury.

Section snippets

Animals

Male normotensive Wistar rats (Wistar EPM-1) weighing approximately 280±8 g were divided into six groups which received deionized water and a special diet containing 18% protein, 4% salt mixture, 1% vitamin mixture, 8% soybean oil 4% fiber and 65% corn starch. The salt mixture was modified to contain three concentrations of magnesium (g/kg chow); normal (1.0), high (2.0) and low (0.3). After three weeks, all animals were anesthetized by intraperitoneal injection of thionembutal (Abbott, 20

Serum magnesium and calcium levels

Serum calcium and magnesium levels determined 15 days after balloon injury were not affected by the high magnesium diet, but the animals fed a low magnesium diet presented the lowest magnesium serum levels, and also the highest ionized blood calcium levels (Table 1).

Histological analysis

Moderate intimal thickening of the thoracic aorta was observed on light microscopy only in the injured specimens. In the balloon-injured groups no significant differences in the ratio of intimal:medial area were observed among the

Discussion

Our results confirm that magnesium deficiency can be established rapidly through the diet [11]. However, magnesium supplementation in the diet did not lead to significant increase on its serum levels. Magnesium serum levels express only 1% of the total magnesium pool [12], a possible reason for this finding. Actually, in some studies, normal magnesium serum levels have been reported even in the presence of evident abnormality 13, 14. The inverse relationship between the magnesium content of the

Acknowledgements

The authors are grateful to Ms Ivete Ueda for assistance with laboratorial analysis, and CEDEME (Centro de Desenvolvimento de Modelos Experimentais para Medicina e Biologia) for providing the animals. This work was supported in part by CNPq (Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico) and a grant from Baldacci Corp.

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The effect of intra-arterial magnesium infusion on endothelium-dependent vasodilation (EDV) in the forearm was studied in nine young healthy students (four men and five women). The EDV was assessed as forearm blood flow (FBF), measured by venous occlusion plethysmography, during infusion of methacholine (MCh). Endothelium-independent vasodilation (EIDV) was defined as FBF during infusion of sodium nitroprusside (SNP). During magnesium infusion in the brachial artery, 0.066 mmol/min, the concentration of ionized magnesium in venous plasma in the infused arm increased by 114%, from 0.59 (SD 0.04) to 1.26 (0.34) mmol/L (P = .0002).
The FBF at baseline (ie, before administration of MCh or SNP) increased from 3.5 (1.1) to 7.3 (3.4) mL/min/100 mL tissue during magnesium infusion (P = .002). During low-dose MCh administration (2 μg/min), FBF increased by 24%, from 15.4 (5.5) to 19.1 (6.8) mL/min/100 mL tissue (P = .04), and during high-dose MCh administration (4 μg/min) FBF increased by 18%, from 20.3 (6.4) to 24.0 (7.2) mL/min/100 mL tissue (P = .04). The EIDV did not change significantly. Systemic blood pressure was not significantly altered by magnesium infusion. No change in FBF either at rest or during infusion of MCh or SNP was observed during the time-control protocol.
In conclusion, this in vivo study showed that intra-arterial magnesium infusion increased EDV in the infused human forearm, which is in accordance with findings in previous in vitro and animal experiments.
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Previous studies have reported the development of vasoconstriction immediately after invasive coronary interventions. Other studies in animals have demonstrated that using oversized balloon angioplasty, vasospasm can be suppressed, even in the presence of endothelial denudation due to important structural alteration in vascular smooth muscle. The regenerated endothelium also appears to be impaired chronically by selective attenuation of in vitro endothelial dependent relaxation related to pertussis toxin-sensitive G proteins. The purpose of this investigation was to verify in vivo and in vitro vasoreactivity to bradykinin (BK) and serotonin (5-hydroxytryptamine; 5-HT) (endothelial dependent agonists) as well as to nitroglycerin (NTG) (exogenous nitric oxide donor) at different times after oversized balloon angioplasty intervention ranging from 1 h to 12 weeks, in normal porcine coronary arteries. BK-induced vasodilatation in vivo was impaired acutely, but it was restored after 4 weeks. Serotonin caused vasoconstriction in vivo that was significantly augmented after 12 weeks. Conversely, endothelium-dependent vasodilatation in vitro to BK and 5-HT remained attenuated during the whole period of follow-up. Finally, relaxation elicited by NTG was reduced in the in vivo experiment until the first week after the procedure. Histological analysis showed severe arterial injury, and complete recovery of endothelial coverage after 4 weeks. In conclusion, this experiment supports evidence for the occurrence of the acute attenuation of vasoresponsiveness and chronic endothelial dysfunction following overstretching coronary balloon angioplasty. Abnormal remodeling associated with the severity of injury may contribute to chronic endothelial dysfunction. Differences found between in vivo and in vitro studies also suggest that multiple endogenous influences present in the former can attenuate the greater endothelial dysfunction demonstrated by endothelial assessment in vitro.
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Dietary magnesium improves endothelial dependent relaxation of balloon injured arteries in rats

Abstract

Introduction

Section snippets

Animals

Serum magnesium and calcium levels

Histological analysis

Discussion

Acknowledgements

J Biol Chem

J Biol Chem

Eur J Pharmacol

Am J Clin Nutr

Biochim Biophys Acta

Eur J Pharmacol

Magnesium deficiency, atherosclerosis and health Care

Diabetes Care

Impaired vascular reactivity following angioplasty is mainly due to endothelial injury

Exp Mol Pathol

Persistent dysfunction of regenerated endothelium after balloon angioplasty of rabbit iliac artery

Circulation

Balloon angioplasty: natural history of the pathophysiological response to injury in a pig model

Circ Res

Biological actions and properties of Endothelium-derived Nitric Oxide formed and release from artery and vein

Circ Res