Biomedical subjects
Publications and source records attributed to A Berthelot.
We have compared a few parameters of magnesium metabolism in spontaneously hypertensive (SHR) and Wistar Kyoto rats (WKY). The results show a decrease of plasma magnesium and urinary magnesium. There is no difference in fecal magnesium and in balance of magnesium. These results have raised a question as to the importance of changes in magnesium metabolism in the mechanism of hypertension.
The effect of diets modified with respect to their calcium content was studied in three models of hypertensive rats: mineralocorticoid hypertension, DOCA + saline rats and genetic hypertension, SHR and LH rats. Normocalcemic control diet, was equilibrated in vitamins and contained 0.6 p. 100 Ca, 0.24 p. 100 Na and 0.6 p. 100 K. Low calcium diet with only 0.03 p. 100 Ca was studied in the SHR from 5 to 10 weeks of age. Calcium enriched diets contained 1.3, 1.2 and 2.5 p. 100 calcium respectively for DOCA (6 to 16 weeks), SHR (5 to 44 weeks) and LH (female rats, 4 to 22 weeks). In the SHR low calcium diet enhanced hypertension. At the opposite in the three models, calcium enriched diet lessened hypertension. The effect appeared within 2 weeks and was long lasting. These results clearly establish that in young hypertensive rat a low calcium diet enhances the development of hypertension and confirm earlier works with calcium enriched diets. Experimental and clinical data from other groups leads us to emphasize the importance of alimentary calcium in the hypertensive pathology.
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Young (5 week old) spontaneously hypertensive rats (SHR) were fed diets modified with respect to their calcium content. Control rats were given a normal calcium diet (0.3 per cent). During the experiment the systolic blood pressure (SBP), heart rate and serum level of total and ionized calcium were measured. Three diets were studied :calcium-free diet (0 per cent, h1), low calcium diet (0.03 per cent, h2) and high calcium diet (1.2 per cent, H). The h1 diet induced a transitory increase (at week 2), then a long-lasting decrease in SBP for 12 weeks. Heart rate and calcemia were significantly decreased. The h2 diet enhanced the increase in SBP and lowered heart rate for 10 weeks. Level of total and ionized serum calcium were unchanged. The high calcium diet (1.2 per cent) attenuated the increase in SBP for 44 weeks and enhanced the heart rate for 16 weeks. The serum level of total calcium remained stable but that of ionized calcium increased significantly at week 7. These data clearly establish that, in young SHR, a low calcium diet enhances the development of genetic hypertension and confirm earlier works obtained with calcium enriched diets. Experimental and clinical data lead us to emphasize the importance of alimentary calcium in the hypertensive pathology.
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.
The aim of the study was to investigate changes in the magnesium balance in DOCA + NaCl (S)-treated rats and the role of the parathyroid and thyroid glands in these changes during such treatment. A large loss of magnesium in the urine is observed during the onset of DOCA + S treatment, but the magnesium balance was higher after 3 weeks of treatment than in normal untreated rats. DOCA + S treatment provoked the same magnesium losses in the urine of rats without a parathyroid gland and without a thyroid gland. However, the magnesium balance was higher in rats still possessing their thyroid gland. Thus, it appears that the thyroid gland is necessary to provoke a gain in the magnesium balance during mineralocorticoid treatment.
In young male rat (Okamoto strain) hypertension develops more rapidly with a low calcium diet (0,03 per cent) and more slowly with a high calcium diet (1,2 per cent). Moreover hypertensive levels are slightly but statistically lessened after 9 months of high calcium diet. It appears that dietary calcium modulates development of genetic hypertension in the Rat.
Parathyroidectomy (PTX) lessens hypertension if performed on young SHR, and on Sprague-Dawley rats, one week before DOCA + NaCl treatment. PTX also increases diuresis and possibly sodium excretion. In this work, sodium balance was investigated during the onset of hypertension, since in SHR and DOCA + NaCl rats, sodium metabolism is related to the level of hypertension. Results show that sodium excretion is enhanced in PTX-DOCA rats immediately after DOCA treatment but lowered in PTX-SHR for 11 weeks. Nevertheless after PTX, sodium balance remains unchanged throughout the experiment. It appears that PTX does not lessen hypertensive development in both models via a decreased sodium balance.
In male Sprague--Dawley rats, hypertensive development was diminished for 10 weeks when parathyroidectomy (PTX) was performed 1 week before deoxycorticosterone plus saline (DOCA + NaCl) treatment. In young spontaneously hypertensive male rats (SHR, Okamoto strain) parathyroidectomy performed after weaning lessened hypertensive levels and lowered heart rate for 24 weeks. When mineralocorticoid or genetic hypertension was established, parathyroidectomy did not significantly change blood pressure levels. High dietary calcium in PTX--SHR rats reestablished normal serum calcium but not systolic blood pressure to the level of sham SHR. From our present and previously reported results, it appears that the parathyroid gland is necessary for the total development of hypertension in both models.
Parathyroidectomy performed on young SHR and on Sprague-Dawley rats, one week before DOCA + saline treatment, lessened hypertension. A possible explanation would be a decreased sodium balance after parathyroidectomy. Data clearly show that there are no significant changes in sodium balance but some variations in urinary sodium excretion.
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.
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.
1 Previous work has shown that parathyroidectomy (PTX) decreases cardiovascular reactivity to noradrenaline in Sprague-Dawley rats with mineralocorticoid-induced (D) hypertension. 2. In order to explain this diminution of cardiovascular reactivity, we studied in vivo the influence of serum calcium levels on the cardiac and vascular response to noradrenaline (500 ng/kg). We used rats with or without parathyroids but fed a standard or a high-calcium (+Ca) diet that re-established a serum calcium level of about 100 mg/l. Work was performed in vagotomized, anaesthetized rats after ganglionic blockage with pentolinium and atropine sulphate. 3 Cardiac output was unchanged in all the experimental groups after 11 weeks of mineralocorticoid treatment. The enhancing effect of noradrenaline was not modified. 4. Since a serum calcium level of about 100 mg/l was sufficient to re-establish vascular reactivity to exogenous noradrenaline in the PTX-D rats, parathyroid hormone was not necessary. 5 The total and lanthanum-resistant calcium fractions of the walls of the aorta were reduced in the PTX-D rats. When serum calcium levels were re-established at about 100 mg/l, there was no difference between PTX-D and D rats. 6 It is postulated that the decreased storage of calcium in vascular smooth muscle cells of PTX-D rats depresses the vascular effect of noradrenaline.
Autografted parathyroids in thyroparathyroidectomized rats reestablished normal calcemia, increased calciuria, but calcium balance remained unchanged. DOCA + Saline effects on calcium metabolism (calciuria and positive calcium balance both increased) are found only when parathyroid and thyroid are present.
Previous work has shown that parathyroidectomy lessens hypertension if performed on young SHR (5-6 weeks of age). In this work, ionic changes (Na+, K+, Ca2+, Mg2+) were studied in heart and aorta during a chronic experimentation. In the heart, atria and ventricle, Ca2+ content was significantly diminished, 15 days after parathyroidectomy. Nevertheless after 8 months, this difference did not remain. A correlation between Ca2+ content and heart rate (lessened immediately after parathyroidectomy) is suggested. In the aorta, parathyroidectomy did not change Na+, K+, Ca2+ and Mg2+ content after 15 days. At the opposite Mg2+ content was significantly lessened after 8 months (-33 p. 100, p less than 0,001). Calcium content in the Lanthanum Resistant Fraction was also depressed significantly at this time. Variations in heart and aorta ionic contents are discussed in relation with hypertensive development.
This study aims to investigate changes in the calcium balance in DOCA-saline treated rats and the effect of parathyroidectomy on these changes during such treatment. However, even with this large loss in calcium, the calcium balance was higher after 2 weeks of treatment than in normal untreated rats. The DOCA-saline treatment provoked greater in normal rats. But the calcium balance became negative after 2 weeks of treatment. Thus, it appears that the presence of the parathyroid gland is necessary to provoke a gain in the calcium balance during mineralocorticoid treatment.
The acute effects of parathyroid extract (PTE) on the cardiovascular system were the object of the study. PTE injected at concentrations of 10--100 U USP/kg into conscious rats induced a rapid, transitory fall in systolic blood pressure and a decrease in the total peripheral resistance. Since the cardiac output was unchanged, PTE must act on vascular smooth muscle. In vitro, PTE (2--16 U USP/ml) inhibited the tonic phase (which requires the presence of extracellular calcium) of the contraction of the thoracic aorta in response to phenylephrine or noradrenaline. 45Ca fluxes in the isolated aorta, measured by the lanthanum method, changed in the presence of a high concentration of PTE (1.0 U USP/ml). After 2 min, the influx was lowered and the efflux was enhanced. These effects may have been specific, since they did not appear when PTE had been previously inactivated. Our results suggest that the vasodilator effect of PTE in the rat is due to an action on Ca exchange in vascular smooth muscle.
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.