Biomedical subjects

A Berthelot

Publications and source records attributed to A Berthelot.

At least 37 records · Page 2Linked to original sources

PubMed1997

Magnesium deficiency increases vasoconstrictor activity without affecting blood pressure of aged spontaneously hypertensive rats.

This study examines the effect of long-term magnesium-deficient diet on blood pressure and vascular reactivity in aged spontaneously hypertensive rats (SHR) with established hypertension. Thirty-one-week old male SHR received control (0.15 per cent magnesium) and magnesium-deficient (0.015 per cent magnesium) diets for 30 weeks. Systolic blood pressure was measured by tail-cuff method. At the end of the study, the heart, aorta and kidney were collected to measure total magnesium and calcium concentrations; the ex vivo effects of the different magnesium diets on vascular reactivity were examined in isolated aorta and in the isolated perfused mesenteric vascular bed. After 30 weeks, magnesium deficiency had no effect on systolic blood pressure and heart rate of SHR. The tissue concentrations of total magnesium in aorta, heart and kidney were not modified by magnesium deficient diet. Total calcium concentration was significantly higher in the heart of the SHR fed the magnesium-deficient diet (p < 0.01). The aortic responsiveness to contractile agents norepinephrine, endothelin-1, CaCl2 and KCl, and to vasorelaxant agents acetylcholine and isoproterenol were not modified by magnesium deficiency. The vasoconstrictor activity to norepinephrine, CaCl2 and KCl was significantly enhanced in the isolated perfused mesenteric vascular bed of magnesium-deficient SHR (p < 0.05). In conclusion, magnesium deficient diet fails to elevate blood pressure in aged SHR maintained on deficiency for 30 weeks despite an enhanced ex vivo vasoconstrictor activity.

Aging↗

PubMed1996

Alterations of myocardial and vascular adrenergic receptor-mediated responses in Escherichia coli-induced septic shock in the rat.

OBJECTIVES: To investigate responsiveness to exogenous catecholamines in rat bacteremic shock by studying both myocardial and vascular functional parameters; to determine in the same study the relationship of these parameters with other relevant biological parameters of the adrenergic pathway, such as myocardial beta-adrenergic receptors and cyclic adenosine monophosphate (cAMP); and to indirectly approach the roles of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide. DESIGN: Experimental, comparative study. SETTING: Laboratory in a university hospital. SUBJECTS: Male Sprague-Dawley rats, weighing 270 to 320 g. INTERVENTIONS: Intravenous injection of live Escherichia coli DH5 alpha (2 x 10(10) organisms/kg) or saline (0.6 mL) and comparison of the two groups. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and heart rate (HR) were recorded, and circulating TNF-alpha concentrations were measured, during the first 3 hrs after E. coli administration. Myocardial and vascular functional parameters were obtained, respectively, from Langendorff-perfused hearts and isolated aortic rings. Adrenergic biochemical parameters (catecholamines, density and affinity of beta-receptors, and isoproterenol-stimulated myocardial cAMP) were determined 3 hrs after E. coli injection. Mean arterial pressure decreased within 5 to 60 mins after bacteria injection and returned to basal levels in the last 2 hrs; HR was unchanged. Serum TNF-alpha concentrations peaked at 120 mins (7333 +/- 672 pg/mL) and were still increased at 3 hrs. Plasma concentrations of epinephrine and norepinephrine were significantly (p < .05) increased. Baseline values for differential left ventricular pressure and coronary flow were significantly (p < .0001, p < .001, respectively) reduced; HR remained unchanged. Isoproterenol induced a similar increase in differential left ventricular pressure and in HR. There was no decrease in the functional myocardial response to adrenergic stimulation. beta-adrenergic receptors were similar in density and in affinity in the two groups. Isoproterenol-stimulated myocardial cAMP was significantly (p < .01) reduced compared with the control group. In aortic rings, bacteria administration significantly (p < .01) shifted the dose-response curve to norepinephrine to the right, both in the presence and absence of endothelium. NG-monomethyl-L-arginine significantly increased the contractions to attain the control level: p < .001 in presence of endothelium; p < .05 in absence of endothelium. CONCLUSIONS: In ex vivo experiments, 3 hrs after E. coli injection, vascular responsiveness was sharply decreased. This impaired response was improved by inhibition of nitric oxide. The heart, nevertheless, was still able to modulate its inotropic and chronotropic response to isoproterenol, even though an impaired beta-adrenergic-receptor stimulation of cAMP was already present.

Animals↗

PubMed1996

Endothelin-1-induced contraction in isolated aortae from normotensive and DOCA-salt hypertensive rats: effect of magnesium.

1. The contractile responses to endothelin-1 and the effect on these of various magnesium concentrations, were studied in isolated aortic rings from normotensive Sprague-Dawley rats and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats. 2. Contractions induced by endothelin-1 were smaller in endothelium-denuded aortae from DOCA-salt hypertensive rats than in those from normotensive rats. The absence of calcium in the medium attenuated endothelin-1-induced contractions of aortae from both normotensive and DOCA-salt rats, but the contraction was greater in aortae from DOCA-salt hypertensive rats. Ryanodine (which inhibits the release of intracellular calcium) inhibited endothelin-1-induced contractions in aortae from DOCA-salt hypertensive rats to a greater extent than in aortae from normotensive rats. 3. A high extracellular magnesium concentration (4.8 mM) attenuated endothelin-1-induced contractions in tissues from DOCA-salt hypertensive rats but not in tissues from normotensive rats. In the absence of calcium, a high concentration of magnesium attenuated endothelin-1-induced contraction in aortae from both normotensive and hypertensive rats. In the presence of ryanodine, a high concentration of magnesium did not modify the contraction in preparations from either strain. 4. Absence of magnesium attenuated endothelin-1-induced contractions in aortae from both normotensive and DOCA-salt hypertensive rats. In the absence of calcium, removal of magnesium totally inhibited endothelin-1-induced contraction in tissues from normotensive rats but had no effect in those from hypertensive rats. In the presence of ryanodine, the lack of magnesium inhibited endothelin-1-induced contractions in aortae from DOCA-salt hypertensive rats but increased the sensitivity to endothelin-1 of aortae from normotensive rats. 5. The presence of endothelium did not modify the effect of high magnesium on endothelin-1-induced contractions in aortae from normotensive and DOCA-salt hypertensive rats. Conversely, the attenuating effect of magnesium removal on endothelin-1-induced contractions did not occur when endothelium was present. 6. In conclusion, endothelin-1-induced contraction was blunted in aortae from DOCA-salt hypertensive rats. The blunted response was related to altered calcium utilization during contraction. Changes in extracellular magnesium concentration differentially alter endothelin-1-induced contraction in aortae from normotensive and hypertensive rats, possibly by interfering with calcium utilization during contraction. Magnesium may be required for the contractile response to endothelin-1 and increasing magnesium may limit the vascular effects of endothelin-1 in blood vessels from DOCA-salt hypertensive rats.

Animals↗

PubMed1996

Effects of long-term high manganese intake on magnesium metabolism in rats.

The effects of long-term high manganese intake on the magnesium metabolism in rats were studied. One group of rats was fed a normal diet and the treated group received a normal diet and distilled water containing 2 g/litre manganese (as MnCl2). Metabolic studies showed that after 11 weeks of treatment, manganese supplementation modified magnesium metabolism by increasing urinary magnesium excretion and decreasing magnesium balance.

Animals↗

PubMed1995

Dietary magnesium supplementation modifies blood pressure and cardiovascular function in mineralocorticoid-salt hypertensive rats but not in normotensive rats.

The purpose of this study was to determine the effect of dietary magnesium supplementation on blood pressure and cardiovascular function of Sprague-Dawley normotensive and mineralocorticoid-salt (DOCA-salt) hypertensive rats. The rats were pair-fed for 5 wk a purified diet containing either a normal or magnesium-supplemented diet (1.5 or 10 g/kg diet). Magnesium supplementation significantly lowered blood pressure levels in hypertensive rats, but not in normotensive rats. Heart rate was not affected in either group. The blood pressure-lowering effect of magnesium supplementation in DOCA-salt hypertensive rats was associated with a lower in vivo cardiovascular reactivity to norepinephrine and angiotensin II. Norepinephrine reactivity in isolated aortae from DOCA-salt hypertensive rats was not modified by magnesium supplementation. However, endothelium-dependent relaxation to acetylcholine was improved and could be related to the release of endothelial relaxant factors. Magnesium supplementation did not affect cardiac hemodynamics in isolated heart from either normotensive or DOCA-salt hypertensive rats. Furthermore, no protective effects upon myocardial ischemia and ventricular arrhythmias were demonstrated. These findings suggest that the lowering effect of magnesium supplementation on blood pressure in hypertensive rats may be related to a vascular effect of magnesium that reduces vascular tone. Mechanisms related to the pathophysiological development of mineralocorticoid-salt hypertension may be involved.

Animals↗

PubMed1994

Influence of endothelium on Mg(2+)-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat.

The aim of this study was to examine the influence of vascular endothelium on the relaxation induced by increased extracellular Mg2+ concentrations on isolated and noradrenaline-precontracted aorta from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and normotensive rats. In Mg(2+)-free physiologic salt solution (PSS), addition of Mg2+ (0.1-6.0 nM) caused concentration-dependent relaxation of noradrenaline-precontracted aorta with intact or disrupted endothelium. Mg(2+)-induced relaxation in intact aorta, however, was less in DOCA-salt hypertensive rats than in normotensive rats. When endothelium was disrupted, Mg(2+)-induced relaxation was depressed in aorta from both DOCA-salt hypertensive and normotensive rats. The same observations were made in presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor nitric oxide (EDRF/NO) biosynthesis. Mg(2+)-induced relaxation following contraction with noradrenaline was significantly less in intact aorta treated with L-NAME from DOCA-salt hypertensive rats than in intact aorta from normotensive rats. Indomethacin did not affect Mg(2+)-induced relaxation in intact aorta from normotensive rats whereas indomethacin significantly increased it in DOCA-salt hypertensive rats. It is concluded that (1) Mg(2+)-induced relaxation can be mediated by endothelium-dependent mechanisms implicating EDRF/NO; (2) the influence of EDRF/NO is more pronounced on the impaired Mg(2+)-induced relaxation of aorta from DOCA-salt hypertensive rats; (3) Mg(2+)-induced relaxation seems masked by vasoconstrictor prostaglandin release in DOCA-salt hypertensive rats; (4) these differences between normotensive and hypertensive rats could be related to the impaired endothelial function in aorta from DOCA-salt hypertensive rats.

Animals↗

PubMed1992

In vivo and in vitro magnesium effects on aortic prostacyclin generation in DOCA-salt hypertensive rats.

To investigate the blood pressure lowering effect of magnesium (Mg2+) in the hypertensive rat, we measured the prostacyclin release (PGI2, as immunoreactive 6-keto-PGF1 alpha) by isolated aortae from normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats fed a control or Mg(2+)-enriched diet. We also studied the in vitro effect of Mg2+ on aortic PGI2 release. The Mg(2+)-enriched diet significantly decreased by 10% blood pressure in DOCA-salt hypertensive rats but not in normotensive rats. The Mg(2+)-enriched diet significantly increased by 122% aortic PGI2 release in DOCA-salt hypertensive rats, but not in normotensive rats. Mg2+ supplementation in the incubation medium (4.8 mM) significantly increased aortic PGI2 release by 94% in DOCA-salt hypertensive rats, but not in normotensive rats. These data suggest that the Mg(2+)-induced attenuation of blood pressure in DOCA-salt hypertensive rats could be linked with the enhanced vascular PGI2 release.

Animals↗

PubMed1992

Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat.

The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats.

Animals↗

PubMed1992

Magnesium and blood pressure. I. Animal studies.

The relationship between experimental magnesium deficiency and blood pressure is complex and still the subject of much debate. The effect of Mg deficiency and blood pressure in Wistar rats receiving a Mg deficient diet (0.080 g/kg) for 40 weeks was examined. Deficient rats, when compared to controls, showed an initial transitory phase of hypotension, followed by normalization of blood pressure and then hypertension beginning after 15 weeks on the deficient diet. During the whole experimental period, heart rate was significantly increased in deficient rats as compared to controls. The fact that hypotension resulting from Mg deficiency of short duration can be inhibited by antihistamines and by indomethacin suggests that various mediators seen during the inflammatory period of Mg deficiency could be involved. Mg deficiency of long duration was accompanied by hypertension. When Mg-deficient rats received the control diet for a period of 3 weeks, Mg supplementation only partially corrected the hypertension. The hypertension was not a consequence of stimulation of the renin-angiotensin system since the plasma renin activity was not modified and ACE activity was reduced. These deficient rats showed a significantly lower vasopressor response to noradrenaline than control rats. Several factors such as increase in collagen, changes in elastin and arterial elasticity, total lipid content, and calcifications may account for the hyporesponsiveness to contractile agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[In vitro study of the role of endothelium on the vasorelaxant effect of magnesium on the aorta from DOCA-salt hypertensive rats].

Vasorelaxant effects of magnesium (Mg) have been described in man and in animal with arterial hypertension. Some studies have shown relationships between extracellular Mg (magnesium e.c.) and endothelial function. So, our study is designed to determine whether elevated extracellular Mg leads to an endothelium-dependent vasorelaxant effect on contractile tension developed by noradrenaline in isolated aorta from DOCA-salt hypertensive rats. Elevated extracellular Mg (4.8 mM) in the bath significantly depressed the dose-response curve to noradrenaline in aorta with endothelium. Following disruption of endothelium, the vasorelaxant effect of elevated extracellular Mg on contractile response to noradrenaline was greatly inhibited. Furthermore, in presence of L. NG nitroarginine (L-NAME) (10(-4) M), inhibitor of endothelial nitric oxide (NO) biosynthesis, the vasorelaxant effect of extracellular Mg on contractility to noradrenaline was partially inhibited. The addition of sodium nitroprussiate (5 10(-9) M), known to spontaneously release NO, caused the reappearance of Mg vasorelaxation which had disappeared in aorta without endothelium. In conclusion, vascular endothelium seems to play an important role in the Mg-induced depressed contractile response to noradrenaline in isolated aorta from DOCA-salt hypertensive rat. Endothelial NO seems to be implicated in the endothelium-dependent action of extracellular Mg.

Animals↗

PubMed1991

Calcium metabolism in the Lyon hypertensive rat.

In order to define relationships between hypertension and calcium metabolism, we have studied calcium metabolism in Lyon genetically hypertensive rats (LH) and their two normotensive controls (LN and LL). The total and ionized plasma calcium levels were slightly but significantly decreased in the LH compared to LN and LL from 4 to 23 weeks of age. During this period, dietary calcium intake was decreased in LH rats but urinary and fecal excretions did not differ. Intestinal utilization and balance were impaired during development of hypertension in LH rats. Thus minor alterations in calcium metabolism differentiate the LH rat from its normotensive controls.

Aging↗

PubMed1988

Effect of moderate magnesium deficiency on serum lipids, blood pressure and cardiovascular reactivity in normotensive rats.

1. Weanling Wistar rats were pair fed for 10 weeks on a purified diet containing either normal or suboptimal quantities of magnesium (960 or 80 mg/kg respectively). 2. At week 2, hypomagnesaemia was accompanied by hypertriglyceridaemia, an increase in plasma cholesterol and a decrease in high-density-lipoprotein-cholesterol in animals fed on the Mg-deficient diet. At week 10, the increase in triglycerides observed in Mg-deficient animals was less marked while the increase in total cholesterol was more important. 3. During the whole experimental period, Mg-deficient animals never showed hypertension. At week 2, mean arterial blood pressure was significantly lower in Mg-deficient rats than in their respective controls, while heart rate was significantly increased. However, hypotension accompanied by tachycardia was a transitory phenomenon which appeared only in the early phase of deficiency. 4. Vascular reactivity was studied in vagotomized anaesthetized rats after ganglionic blockade with pentolinium and atropine sulphate. The reactivity to noradrenaline was significantly higher in Mg-deficient rats compared with pair-fed controls after 2 weeks on the experimental diet.

Animals↗

PubMed1988

Effects of high magnesium intake on central catecholamines in spontaneously hypertensive rat.

Spontaneously hypertensive rats (SHR) received a highly magnesium enriched diet during the development of hypertension, which caused plasma Mg concentrations to be markedly increased. Arterial blood pressure was reduced in supplemented animals. Levels of noradrenaline, 3-dihydroxyphenylacetic acid and homovanillic acid in cortex, hypothalamus, striatum and brain stem remained unchanged. Dopamine levels in the cortex, hypothalamus and striatum were also unchanged. Dopamine levels in brain stem increased. However the correlation between treatment with magnesium, dopamine-related variables in the brain and decrease in blood pressure in SHR remains hypothetical.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Trace elements during the development of hypertension in the spontaneously hypertensive rat.

Total plasma concentrations of bromine, copper, rubidium, selenium and zinc were measured in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) of 5-20 weeks of age, using an X-ray fluorescence spectrometry technique. Although plasma levels of bromine, rubidium, selenium and zinc varied at different ages when comparing SHR and WKY, their general evolution was similar. Copper levels increased more in SHR than in WKY. These perturbations in trace element levels could perhaps participate in the establishment of hypertension in SHR, but could also be due to genetic differences between the strains, unrelated to the development of hypertension.

Animals↗

PubMed1987

Disturbances of magnesium metabolism in the spontaneously hypertensive rat.

Magnesium balance, and plasma and urinary levels, were studied in spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and in Wistar (WI) rats. We found few differences in the measured parameters between WKY and WI rats, but the SHR rat which similarly maintained Mg balance has lower plasma Mg levels and less urinary Mg excretion. These abnormalities could favor establishment or maintenance of hypertension.

Animals↗

PubMed1987

[Major thrombopenia induced by heparin. Practical approach to cardiac surgery under extracorporeal circulation].

Major heparin-induced thrombocytopaenia (HIT) is a condition which is feared more for its thrombotic complications than for the risk of haemorrhage. The platelet count is part of routine surveillance of patients receiving this treatment which must be withdrawn if HIT occurs. The use of heparin remains essential for cardio-pulmonary bypass surgery. There are two possible scenarios: The thrombocytopaenia occurs in the postoperative period: the standard heparin may be relayed by oral anti-vitamin K anticoagulants, platelet antiaggregant drugs or by low molecular weight heparin (LMWH). The diagnosis of HIT is made before surgery: three therapeutic attitudes are discussed with respect to the urgency of surgery: surgery is deferred for 6 to 8 weeks to allow the platelet count to return to normal and the responsible circulating antibody to disappear; the use of LMWH providing the tests of platelet aggregation are negative with this product; in addition, there are other problems specific to their use in cardiopulmonary bypass to be considered; blood exchange at the beginning of cardiopulmonary bypass to eliminate the circulating factor responsible and so allow the use of standard heparin during and after the operation: this is the only possible solution in cases with in vitro aggregant activity of LMWH.

Cardiac Surgical Procedures↗

PubMed1987

Blood pressure and plasma renin activity after magnesium supplementation in the spontaneously hypertensive rat: a study during developing and established hypertension.

The effects of a dietary magnesium supplementation have been studied both on systolic blood pressure and plasma renin activity in the spontaneously hypertensive rat (SHR). This study has been conducted in young (developing hypertension) and mature (established hypertension) male SHR fed during 6 weeks with a normal magnesium diet or with a high magnesium diet. After 6 weeks of diets, the systolic blood pressure was lower in young and mature SHR fed with an increased dietary amount of magnesium than in the young and mature SHR fed with a normal amount of dietary magnesium. Plasma renin activity was similar after the two different diets in young SHR while it was greater in mature SHR receiving a high magnesium diet than in mature SHR receiving a normal diet. Hence, dietary supplementation with magnesium inhibits the development of hypertension in young SHR, and reduces arterial blood pressure in mature SHR. The hypotensive effect observed during magnesium supplementation is not related to an inhibition of the renin release.

Age Factors↗

PubMed1986

[Dietary magnesium and mineralocorticoid DOCA-salt hypertension in the rat. Effect on the metabolism of sodium and magnesium].

The effects of a diet enriched in magnesium were studied in mineralocorticoid DOCA-salt hypertensive rats from 6 to 15 weeks old, during the development of hypertension. A standard normomagnesic diet with 0.21% Mg and 0.24% Na, equilibrated in minerals and vitamins is used as a control diet. The high magnesium diet is the same standard diet enriched in magnesium with a content of 0.75% Mg. That in magnesium enriched diet lessens the level of blood pressure. This effect appears within 2 weeks and is long lasting. Increase of urinary sodium is observed but without any modification of sodium balance. Sodium plasma is not changed. Plasma, urinary and balance of magnesium are increased. These results establish that in mineralocorticoid DOCA-salt hypertension, a high magnesium diet decreases hypertension. The observed metabolic variations may perhaps explain the protective effect of this in magnesium enriched diet.

Animals↗