Training-induced anti-atherosclerotic effects are associated with increased vascular PPARgamma expression in apolipoprotein E-deficient mice.

AIM: Physical exercise prevents cardiovascular risk and atherosclerosis lesions. However, the molecular aspects are still unknown. Vascular peroxisome proliferator-activated receptors (PPARs) exert anti-atherogenic effects. The aim of this study was to determine whether exercise-induced anti-atherosclerotic effect is associated with change in PPARs vascular expression in apolipoprotein E-deficient (ApoE(-/-) ) mice. METHODS: Male ApoE(-/-) mice were fed with a high-fat diet and randomized into two groups: one trained group undergoing swimming training for 3 months and one sedentary group. Sedentary and trained C57BL/6J mice were used as control. mRNA of PPAR-α, PPAR-ß/δ and PPAR-γ was measured in aorta by quantitative PCR. mRNA of pro- (TNF-α, IL-1ß) and anti-inflammatory (IL-10, IL-1Ra) cytokines was also measured. RESULTS: Atherosclerotic lesion size was significantly reduced in trained ApoE(-/-) mice compared to sedentary ones. In contrast, reduction of atherosclerotic lesion size was not observed in trained ApoE(-/-) mice supplied with BADGE, an antagonist of PPAR-γ. Exercise training significantly increased PPAR-γ expression in aorta. PPAR-γ expression was inversely correlated with the atherosclerotic plaque area. Aortic PPAR-α and PPAR-ß/δ mRNA expressions were not changed in response to exercise training. Atherosclerosis increased the aortic mRNA expression of TNF-α, IL-1ß, IL-10 and IL-1Ra. Exercise training decreased aortic IL-1ß mRNA expression in ApoE(-/-) mice, but did not change expression of TNF-α, IL-10 and IL-1Ra. IL-1ß mRNA expression was also significantly lower in atherosclerosis lesions from trained ApoE(-/-) compared with those from sedentary ones. CONCLUSIONS: Exercise training increases vascular PPAR-γ expression in ApoE(-/-) mice that could potentially underlie training-related beneficial effects on atherosclerosis.

Late effects of cycle competition on arterial stiffness. A preliminary study.

AIM: The purpose of this study was to examine the effects of a cycle competition on the large arteries stiffness, 24-hours after the end of the effort. METHODS: Two males elite cyclists were studied before and after performing a stage-race. Their heart rate (HR) was measured continuously during the two competition days. The impact of the competition on their vascular system was determined using the measure of pulse wave velocity (PWV), an index of regional arterial stiffness. HR and blood pressure were also measured before and 24-hours postexercise. RESULTS: During the race, mean cyclists HR were relatively similar. Changes in PWV and HR were found after competition: these measures increased for the offensive subject and decreased for the other. CONCLUSIONS: Despite their involvement in the same cycling competition, we suggest that the long-term effects induced by effort on arterial stiffness were inverted according to the subject's comportment during the race. This study should be completed by others measures in order to precise our results and to precise the possible link between arteries stiffness and the recovery kinetic process, both depending on the cardiovascular autonomic nervous system control.

Physiological and pathophysiological role of magnesium in the cardiovascular system: implications in hypertension.

Attention is growing for a potential role of magnesium in the pathoetiology of cardiovascular disease. Magnesium modulates mechanical, electrical and structural functions of cardiac and vascular cells, and small changes in extracellular magnesium levels and/or intracellular free magnesium concentration may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Thus, magnesium may be important in the physiological regulation of blood pressure whereas alterations in cellular magnesium metabolism could contribute to the pathogenesis of blood pressure elevation. Although most epidemiological and experimental studies support a pathological role for magnesium in the etiology and development of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of essential hypertension is unclear. The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells. In addition, alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic effects of magnesium are addressed.

Dietary magnesium intake can affect mechanical properties of rat carotid artery.

The purpose of the present study was to determine the effects of Mg deficiency and supplementation on the mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously using an echo-tracking device. Systolic, diastolic and mean intra-arterial pressures were not significantly different in Mg-deficient, -supplemented or control rats. Histological examination showed a larger cross-sectional area, increased intima-media thickness and a greater media:lumen value in carotid artery of Mg-deficient rats, indicating that Mg deficiency may directly stimulate growth and/or proliferation of arterial wall components. In addition, we observed a negative linear relationship between intima-media thickness and plasma Mg concentration, suggesting that increased Mg intake may counteract arterial wall hypertrophy. Neither Mg deficiency nor supplementation modified the arterial distensibility v. intra-arterial pressure curve or the E(inc) v. wall stress curve, indicating that dietary Mg intake did not modify wall stiffness in young rats. At mean intra-arterial pressure, the stress and E(inc) values were, however, significantly lower in Mg-deficient rats (p < 0.05 in both cases); this finding could be related to the alteration in the geometry of the carotid artery. In conclusion, these findings suggest that Mg deficiency modifies the mechanical properties of the common carotid artery in young rats. Since Mg deficiency is considered a risk factor, these mechanical alterations could contribute to the development of atherosclerosis, hypertension and cardiovascular diseases.

Effect of magnesium deficiency on blood pressure and mechanical properties of rat carotid artery.

The purpose of this study was to determine the effect of dietary Mg deficiency (80 mg/kg versus control diet: 960 mg/kg) on blood pressure and mechanical properties of the rat common carotid artery. The internal diameter and intra-arterial pressure of carotid artery were measured continuously with an echo-tracking device. At 19 weeks, systolic, diastolic, and mean blood pressures were higher in Mg-deficient rats. Histological examination showed an increase in cross-sectional area, intima-media thickness, and media-to-lumen ratio in carotid artery of Mg-deficient rats. Mg deficiency did not modify the arterial distensibility-blood pressure curve. At mean blood pressure, arterial distensibility was significantly less in 19-week-old rats than in 5-week-old rats of both control and Mg-deficient groups. A significant interaction between age and Mg-deficient diet on arterial distensibility (P<0.04) indicates an accelerated age-dependent decreased arterial distensibility with Mg deficiency. At 19 weeks, the artery was stiffer in hypertensive Mg-deficient rats, as illustrated by a shift to higher levels of the incremental elastic modulus-stress curve. In conclusion, the increased blood pressure and the vascular morphological alterations observed in Mg-deficient rats may contribute to an accelerated alteration of the wall material, which in turn leads to a stiffening of the carotid artery.

Time-course of the change in blood pressure level in magnesium-deficient Wistar rats.

The aim of the present study was to determine whether a severely Mg-deficient diet can modify blood pressure in rats and whether these alterations in blood pressure are associated with a change in in vivo cardiovascular reactivity, alteration in plasma lipids and modification of the production of hormones involved in blood pressure regulation. Weanling male Wistar rats were pair-fed for 40 weeks with control (960 mg Mg/kg) and Mg-deficient (80 mg Mg/kg) diets. At 2 weeks, blood pressure was lower in Mg-deficient rats, while heart rate was greater than in controls. Mg-deficiency-induced hypotension was transitory and the administration of antihistamine agents inhibited the appearance of this hypotensive phase, suggesting that histamine may play a role in lowering blood pressure. Until 15 weeks, blood pressures were similar for control and Mg-deficient rats. Thereafter, blood pressure rose gradually until the end of the experiment in Mg-deficient rats. Heart rate remained higher in hypertensive Mg-deficient rats. After 21 weeks, in vivo cardiovascular reactivity to noradrenaline was lower and reactivity to angiotensin II was unchanged in hypertensive Mg-deficient rats. At 2 and 21 weeks, hypomagnesaemia was accompanied by higher plasma levels of Ca, triacylglycerols and cholesterol. Plasma renin activity was higher at week 2, whereas levels of plasma angiotensin converting enzyme were lower at 2 and 21 weeks in Mg-deficient rats. The plasma aldosterone level was higher at 2 and 21 weeks while the vasopressin level did not change. Plasma corticosterone levels were lower at 2 weeks and higher at 21 weeks. It is concluded that Mg deficiency induced a transitory hypotension followed by a sustained hypertension in rats. The release of vasodilator inflammatory agents may contribute to the early hypotension. The hypertensive phase may be explained by the increased sympathetic nervous activity induced by Mg deficiency even though the contribution of several hormonal systems implicated in blood pressure regulation remains to be elucidated.

Effects of propofol on vascular reactivity in isolated aortae from normotensive and spontaneously hypertensive rats.

We have investigated the effects of propofol 50 mumol litre-1 on contractile and relaxant responses in experimental hypertension and assessed endothelial modulation of these responses. Propofol attenuated norepinephrine-induced contraction of endothelium-intact and endothelium-denuded rings from both Wistar Tokyo (WKY) and spontaneously hypertensive rats (SHR). The effect was significantly greater in endothelium-intact aortae from SHR than in those from WKY rats. Propofol markedly attenuated AVP-induced contraction in aortae from both WKY and SHR. Propofol attenuation of norepinephrine contraction was also observed in rings from both SHR and WKY rats incubated with L-NAME. Propofol attenuation of norepinephrine contraction was suppressed by indomethacin in aortae from SHR but not in those from WKY rats. These results suggest that: (1) propofol attenuated vascular contraction of isolated aortae from SHR in part by a mechanism dependent on events distal to the receptor site (norepinephrine, arginine vasopressin); (2) the effect of propofol on contraction in SHR, observed in the presence of nitric oxide synthase inhibitors but not cyclooxygenase inhibitors, was consistent with either propofol induction of vasodilating cyclooxygenase metabolites from the endothelium or propofol inhibition of vasoconstricting cyclooxygenase metabolites.

Effect of age on in vitro magnesium modulation of vascular reactivity in the rat aorta.

Vascular reactivity and the effect of various magnesium (Mg) concentrations on it, were studied in aortic rings from adult (4-month-old) and aged (24-month-old) male Sprague-Dawley rats. Contraction induced by CaCl2 of the aortae incubated in high potassium PSS containing 1.2 mM Mg was greater in aged than in adult rats. Low Mg (0.1 mM) decreased CaCl2-induced contraction in the aortae from adult rats more than in those from aged rats. High Mg (4.8 mM) attenuated CaCl2-induced contraction in the aged but not in the adult rats. Acetylcholine- and isoproterenol-induced relaxation of the aortae incubated in normal PSS (1.2 mM) was less pronounced in aged than in adult rats, whereas sodium nitroprusside-induced relaxation was similar in both groups. Low Mg did not modify acetylcholine- and sodium nitroprusside-induced relaxation in adult and aged rats. With high Mg, acetylcholine- and sodium nitroprusside-induced relaxation was increased in both groups. The increasing effect of high Mg on acetylcholine-induced relaxation was however greater in aorta from aged rats. Low Mg decreased isoproterenol-induced relaxation in the adult but not in the aged group, whereas high Mg increased it in both groups of rats. When endothelium was intact, Mg-induced relaxation was less in aged than in adult rats. When endothelium was disrupted, relaxation was similar in both groups . Mg Removal produced an endothelium-dependent relaxation, which was significantly lower in the aged rats. In conclusion, the functional alterations of vascular smooth muscle and endothelium observed with aging modify the modulatory role of Mg on aortic responsiveness.

Effect of magnesium on calcium responses to vasopressin in vascular smooth muscle cells of spontaneously hypertensive rats.

This study investigated the modulatory effect of magnesium (Mg++) on basal and agonist-stimulated intracellular free calcium (Ca++) concentration ([Ca++]i) in vascular smooth muscle cells from spontaneously hypertensive rats (SHR). Effects of increasing extracellular Mg++ concentration ([Mg++]e) on vasopressin (AVP)-induced [Ca++]i responses were determined in primary cultured unpassaged vascular smooth muscle cells from mesenteric and aortic vessels (representing resistance and conduit arteries, respectively) of Wistar Kyoto rats (WKY) and SHR. [Ca++]i was measured by fura-2 methodology. Underlying mechanisms for Mg++ actions were determined in Ca(++)-free buffer and in the presence of diltiazem (10(-6) M), an L-type Ca++ channel blocker. Basal and AVP-stimulated [Ca++]i responses were significantly increased (p < .05) in SHR (pD2 = 8.3 +/- 0.1, Emax = 532 +/- 14 nM for SHR; pD2 = 8.0 +/- 0.04, Emax = 480 +/- 15 nM for WKY). [Mg++]e dose-dependently reduced basal and agonist-induced [Ca++]i responses. High [Mg++]e (4.8 mM) attenuated [Ca++]i responses to AVP in WKY (Emax = 328 +/- 30 nM) and SHR (Emax = 265 +/- 27 nM) and normalized AVP-elicited hyper-responsiveness in SHR (pD2 in high [Mg++]e, 8.1 +/- 0.3 for SHR, 7.8 +/- 0.6 for WKY). Extracellular Ca++ withdrawal and diltiazem abolished the attenuating effects of high [Mg++]e in WKY but not in SHR. These findings demonstrate that Mg++ dose-dependently reduces [Ca++]i and that high [Mg++]e attenuates AVP-stimulated [Ca++]i responses and normalizes sensitivity to AVP in SHR. In WKY, Mg++ actions are dependent primarily on Ca++ influx through L-type Ca++ channels, whereas in SHR, the modulatory effects of [Mg++]e are mediated both by Ca++ influx through Ca++ channels and by intracellular Ca++ release.

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.

Effect of magnesium on vascular tone and reactivity in pressurized mesenteric resistance arteries from spontaneously hypertensive rats.

This study examines the effects of magnesium on vascular tone and reactivity in mesenteric resistance arteries from 17-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Third-order branches of mesenteric arteries were mounted in a pressurized flow chamber and studied with constant flow and transmural pressure. The mesenteric arteries were perfused extra- and intra-luminally with physiological salt solution containing a normal (1.2 mmol/L), high (4.8 mmol/L), or low (0.15 mmol/L) magnesium concentration. Vascular reactivity to norepinephrine and vasopressin was examined when the agonists were applied extraluminally. High magnesium increased lumen diameter and decreased media thickness whereas low magnesium decreased lumen diameter and increased media thickness in mesenteric arteries from both SHR and WKY rats. The effects of magnesium on vascular tone were less in arteries from SHR compared with normotensive controls (p < 0.05). Low magnesium potentiated norepinephrine-induced vasoconstriction in SHR (p < 0.001) but not in WKY. Low magnesium did not modify vasopressin-induced vasoconstriction in either SHR or WKY. High magnesium attenuated vasopressin- and norepinephrine-induced vasoconstriction in SHR (p < 0.01), whereas high magnesium attenuated only norepinephrine-induced vasoconstriction in WKY (p < 0.001). These data suggest that magnesium has differential modulatory effects on vascular tone and reactivity in mesenteric resistance arteries of SHR and WKY. Magnesium may play an important role in the modulation of peripheral resistance in hypertension.

Effect of pressurization on mechanical properties of mesenteric small arteries from spontaneously hypertensive rats.

The mechanical properties of the wall of isolated perfused arterial segments of mesenteric small arteries from 17-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY) were investigated. Third-order branches of mesenteric arteries were mounted in a pressure myograph chamber and pressurized from 1 to 140 mm Hg. Under isobaric conditions, the outer diameter and the lumen of small arteries studied were smaller in SHR than in WKY, whereas media width, media cross-sectional area and media-lumen ratio were greater in SHR. Under passive conditions, the total change in internal and external diameter in response to increasing intravascular pressure was smaller in arteries from SHR. Incremental distensibility was significantly lower in arteries of SHR at intravascular pressures between 1 and 40 mm Hg, but was significantly greater between pressures of 40-100 mm Hg. Wall stress generated by intravascular pressure was significantly smaller in arteries from SHR. As a function of wall strain (under isometric conditions), stress and incremental elastic modulus were shifted to the left in SHR vessels. Under isobaric conditions or in relation to wall stress, the slope of elastic modulus was smaller in SHR. This decrease in elastic modulus may confer additional elasticity to the vascular wall of resistance arteries from SHR. The presence of a greater distensibility at physiological levels of intravascular pressure and decreased incremental elastic modulus indicates that the changes in the structure of small mesenteric arteries in SHR can be defined as the result of a combination of eutrophic and hypertrophic remodeling.

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.

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.

Dietary L-arginine attenuates blood pressure in mineralocorticoid-salt hypertensive rats.

The present study was designed to investigate the influence of dietary L-arginine supplementation on blood pressure and on ex vivo vascular reactivity in mineralocorticoid-salt (DOCA-salt) hypertensive rats. Systolic blood pressure and heart rate were determined throughout the experimental period in unanaesthetized rats. Plasma and urine electrolyte levels were measured. Vasoconstrictor response to noradrenaline and vasodilator responses to acetylcholine and sodium nitroprusside were evaluated in the isolated perfused mesenteric vascular bed. DOCA-salt hypertensive rats were divided into 2 groups: a control group and a treated group receiving 0.8% L-arginine supplementation in drinking water. Dietary L-arginine supplementation attenuated systolic blood pressure in conscious DOCA-salt hypertensive rats, but did not modify heart rate. Plasma calcium and sodium concentrations and urinary magnesium excretion were decreased by L-arginine supplementation. Noradrenaline-induced vasoconstriction decreased and acetylcholine-induced vasodilatation increased, whereas sodium nitroprusside-induced vasodilatation was not modified, in the L-arginine-supplemented rats. It is concluded that dietary L-arginine supplementation in the diet lowers systolic blood pressure in DOCA-salt hypertensive rats, probably through vascular action.

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.

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.

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.

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.

[In vitro study of the role of endothelium on the vasorelaxant effect of magnesium on the aorta from DOCA-salt hypertensive rats]. / Etude in vitro du rôle de l'endothélium sur l'effet vasorelaxant du magnésium sur l'aorte de rat, soumis à une hypertension minéralocorticoïde.

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.