Effects of aqueous hop (Humulus Lupulus L.) extract on vascular reactivity in rats: mechanisms and influence of gender and hormonal status.

Phytoestrogens, naturally occurring plant compounds having oestrogenic and/or anti-oestrogenic activity, are present in many human foodstuffs including hop. Moderate intakes of isoflavonoid phytoestrogens have been associated with a reduction in cardiovascular diseases incidence. So, it is possible that hop (Humulus Lupulus L.) might similarly contribute to the reported health-beneficial effects of moderate beer consumption. Thus, the purpose of this study was to investigate in vitro effects of aqueous hop extract on thoracic vascular reactivity in Sprague Dawley male and female rats. Endothelium-intact thoracic arterial rings from male rats (MALE, n=8), sham-ovariectomized (Sham OVX) female (n=8) and ovariectomized (OVX) female rats (n=8) were used. We assessed the relaxation induced by aqueous hop extract (10(-9), 10(-2)g/l) in aortic rings precontracted with norepinephrine (10(-7)M), in the absence or in the presence of l-NAME (10(-4)M), indomethacin (10(-5)M), thapsigargin (10(-4)M), iberiotoxin (3.10(-8)M), apamin (3.10(-8)M) and TEA (3.10(-4)M). Aqueous hop extract induced relaxation of endothelium-intact thoracic arterial rings in MALE and Sham OVX rats, whereas a weak effect was observed in OVX rats. This vasorelaxation was strongly inhibited in presence of l-NAME, indomethacin and thapsigargin. These data indicated that aqueous hop extract-induced vasodilation, in male and intact female rats, is mediated by NOS activation, cyclooxygenase products and Ca(2+) pathways. Moreover, our results suggested that effect of hop in enhancing vascular reactivity was independent of gender but strongly related to hormonal status.

Effect of diets with different magnesium content in ischemic stroke rats.

Rats fed with low (0.015%), normal (0.08%) or high (0.32%) magnesium (Mg) diet for 5-6 weeks were subjected to photothrombosis-induced infarction. As compared to normal diet, Mg deprivation increased by 45% infarct volume at 24 h after photothrombosis but did not modify the lesion at 4 h after photothrombosis. Mg supplementation did not protect from infarction whatever the time point examined. No differences in pre-ischemic systolic blood pressure and glycemia as well as in post-ischemic kaliemia, calcemia and plasma antioxidant activity were observed between groups. However, plasma total Mg level correlated with plasma antioxidant activity at 4 h after photothrombosis. These results demonstrate that brains from Mg deficient rats are more susceptible to permanent focal ischemia than rats fed with normal or high Mg diet.

Clofibric acid or diethylmaleate supplemented diet decrease blood pressure in DOCA-salt treated male Sprague Dawley rats--relation with liver antioxidant status.

The effects of 8-week diethylmaleate (DEM) and clofibric acid (CFA) supplemented diet on blood pressure, body and liver weights, liver antioxidant status and nitric oxide synthase (NOS) activity were investigated in 8-week DOCA-salt treated and untreated Sprague-Dawley male rats. It appeared that DEM and particularly CFA treatments were associated with a significant decrease in blood pressure in DOCA-salt treated rats, and an accentuation of the decreases in body weights in both diet supplemented groups. This was not associated with increases in NO production in the liver. In contrast, hepatic lipid peroxidation was significantly decreased in both DOCA-salt treated and untreated groups on DEM and particularly on CFA supplemented diet. The protective effects of CFA and DEM against hepatic cellular damage could be involved in the decreases in blood pressure in DOCA-salt treated rats, where CFA was more efficient than DEM. In CFA supplemented groups, there was a strong increase in hepatic superoxide dismutase (SOD), glutathione-peroxidase (GSH-Px), and catalase (CAT) activities and in DEM supplemented groups, increases in SOD and CAT activities and in GSH levels were observed. Our data suggest that normalization of blood pressure in DOCA-salt treated rats by CFA was due to an enhancement of the half-life of NO while DEM increased its availability.

Increased arginase activity in aorta of mineralocorticoid-salt hypertensive rats.

The present study was designed, first to investigate aortic arginase activity during the development and the establishment of mineralocorticoid-salt (DOCA-salt) hypertension, and second, to determine the relationship between arginase activity and blood pressure by giving a protein-supplemented diet (50% casein) known to increase hepatic arginase activity. Our results showed that aortic arginase activity in established hypertension of DOCA-salt rats was higher than in normotensive rats. The protein-supplemented diet (50% casein) accelerated the development of DOCA-salt hypertension. There was a positive correlation between arginase activity and the level of blood pressure in these DOCA-salt hypertensive rats fed 50% casein but not in DOCA-salt hypertensive rats on a normal (20% casein) diet. In normotensive rats, the protein-supplemented diet decreased aortic arginase activity and produced no change in systolic blood pressure. Our data suggest that aortic arginase activity is modified in established DOCA-salt hypertension and could participate in the physiopathology of arterial hypertension.

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.

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 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.

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.

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)

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.

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.

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.

Effects of dietary magnesium on the development of hypertension in the spontaneously hypertensive rat.

The effect of varying the amount of dietary magnesium on the development of hypertension in spontaneously hypertensive (SH) rats was investigated with three diets containing 1.05% (H1Mg diet), 0.52% (H2Mg diet), and 0.008% (LMg diet). The control group was given a diet containing a normal amount of magnesium (0.2%). When the diet was sufficiently supplemented with magnesium (H1Mg diet), the development of hypertension was significantly slowed and the heart rate slightly lowered. With dietary magnesium depletion (LMg diet), the heart rate was accelerated and hypertension developed more rapidly. Excretion of urinary electrolytes (calcium, magnesium, and sodium) was increased by rats fed the H1Mg diet and decreased by rats on the LMg diet. Urinary cAMP was decreased both on the HMg diets and on the LMg diet. With the H1Mg diet, total and ionized calcium and sodium levels in plasma fell, and magnesium plasma levels rose. Rats fed the LMg diet had increased total and ionized calcium and decreased magnesium plasma levels. These results show that dietary magnesium modifies the metabolism of calcium, sodium, magnesium, which can modulate the development of genetic hypertension.

Parathyroids, thyroid and development of hypertension in SHR.

Parathyroid glands play a significant role in the development of hypertension in spontaneously hypertensive rat (SHR), like in deoxycorticosterone acetate (DOCA) + NaCl model. Parathyroidectomy (PTX) performed after weaning delayed systolic blood pressure (SBP) increase and slowed heart rate (HR) in SHR for 42 weeks. These changes could not be attributed to decrease of serum calcium in PTX animals since supplementation of calcium, rendering serum calcium normal, did not reestablish SBP and HR to those of sham SHR. Moreover, in the thyroparathyroidectomized (TPTX) animals SBP and HR were increased by autotransplantation of parathyroids. When hypertension was established (week 15), PTX produced no more changes on cardiovascular parameters measured. These data clearly indicate that independent of thyroidectomy, PTX leads to a lesser degree of hypertension in young SHR, but was without effect on established hypertension. In conclusion, parathyroid glands are required for total development of the hypertensive process in SHR.

Parathyroid hormone- and deoxycorticosterone acetate-induced hypertension in the rat.

1. Hypertension induced by treatment with deoxycorticosterone acetate and sodium chloride was studied in male Sprague-Dawley rats and related to parathyroid hormone secretion. 2. Lack of parathyroid hormone (due to parathyroidectomy) or decreased parathormone secretion (due to a high-calcium diet) partially inhibited the development of arterial hypertension. 3. In contrast, in thyroparathyroidectomized rats supplemented with thyroxine, the administration of parathyroid hormone rapidly elevated arterial blood pressure. 4. Maintaining a physiological concentration of serum calcium in the absence of parathyroid hormone (by feeding a high-calcium diet to parathyroidectomized rats) was not sufficient to establish mineralocorticoid hypertension. 5. These results show that parathyroid hormone is necessary for the complete development of mineralocorticoid hypertension.

[The parathyroids and desoxycorticosterone acetate induced arterial hypertension in the rat]. / Parathyroïdes et hypertension artérielle à l'acétate de désoxycorticostérone chez le rat.

We studied the importance of parathyroids in the development of mineralocorticoid hypertension in male Sprague-Dawley rats. Ablation of the parathyroids 1 week before deoxycorticosterone acetate (DOCA) + NaCl administration prevented development of hypertension (for 1 year). But ablation of parathyroids 2 weeks after the start of treatment has no effect on the development of arterial hypertension. Autotransplantation of parathyroids in thyroidectomized rats caused a recurrence of mineralocorticoid hypertension, which was completed after DL-thyroxine supplementation: blood pressure levels were nearly the same as in DOCA sham rats. We conclude that parathyroid glands favor the establishment of mineralocorticoid hypertension in the rat. These results raise the question of the mechanism of action of parathyroid hormone in the hypertensive process.

[Calcium metabolism and mineralocorticoid-induced hypertension: effects of parathormone and exogenous thyrocalcitonin and of variations in dietary calcium and magnesium]. / Métabolisme calcique et hypertension minéralocorticoïde: effets de la parathormone et de la thyrocalcitonine exogènes et des variations de l'apport en calcium et en magnésium.

Physiological doses of parathyroid extract producing normal serum calcium level restore mineralocorticoid hypertension development in parathyroidectomized or thyroparathyroidectomized rats, supplemented with thyroid hormones. On the other hand, increased calcium or magnesium in dietary moderates hypertension development. Those results confirm the participation of parathyroids during mineralocorticoid hypertension.