The effect of infinitesimal drug dilutions on the pharmacokinetics of nalidixic acid and atenolol.

1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects received three treatments: a single 100 mg oral dose of atenolol (AT) followed 3 h later by either placebo or a dilution of AT (AT 7CH) or of bisoprolol (BI 7CH). The homoeopathic preparations were administered by the sublingual route. 3. In the first NA experiment NA 7CH significantly shortened the elimination half-life of NA from 8.6 +/- 2.2 (placebo) to 6.4 +/- 1.6 h (NA 7CH). In the second NA experiment none of the pharmacokinetic parameters was modified significantly by the administration of NA 7CH. Neither AT 7CH nor BI 7CH modified the pharmacokinetics of AT.

[The sympathetic and renin-angiotensin systems are complementary in blood pressure regulation]. / Les systèmes sympathique et rénine angiotensine se complètent pour contrôler la pression artérielle.

The consequences of a chronic destruction of sympathetic nerves or of the blockade of the renin angiotensin system (RAS) on the blood pressure (BP) level and its spontaneous variability were studied using a computerized method which allows a continuous monitoring of BP in conscious unrestrained rats. Guanethidine, used to lesion the sympathetic fibres did not alter the BP level but significantly enhanced its variability. On the opposite, angiotensin converting enzyme inhibition decreased the BP level without changing its variability. It is concluded that both systems play a complementary role as the RAS determines the long-term BP level while the sympathetic nerves control its short-term variability in conscious animals.

Antihypertensive effect of thromboxane A2 receptor blockade in genetically hypertensive rats of the Lyon strain.

In order to determine whether the increased renal biosynthesis of thromboxane A2, observed in young genetically hypertensive (LH) rats of the Lyon strain, could be involved in the development of their hypertension, 12 LH female rats were given a specific thromboxane A2 receptor antagonist, AH 23848 (Glaxo Group Research) orally (2 mg/kg twice a day) from 3 to 9 weeks of age. In addition, 12 LH and 12 normotensive (LN) rats were given vehicle only (sodium bicarbonate 8%). The thromboxane receptor antagonist AH 23848, which inhibited platelet aggregation by about 65%, did not modify the renal production of thromboxane A2, prostaglandin I2 (PGI2) or prostaglandin E2 (PGE2). It induced a progressive, potent and long lasting decrease in systolic blood pressure which was normalized in 6-, 7- and 8-week-old LH rats, thus demonstrating the involvement of thromboxane A2 in the onset of hypertension in this model. In contrast with thromboxane synthetase inhibitors, the AH 23848 antihypertensive effect persisted 1 week after the cessation of treatment, showing the superiority of thromboxane A2 receptor blockade over thromboxane synthetase inhibition.

Rate of tryptophan hydroxylation in vivo in brain nuclei of genetically hypertensive rats of the Lyon strain.

The rate of tryptophan hydroxylation in vivo is unaltered in brain areas of 5, 9 and 21 week-old Lyon genetically Hypertensive (LH) rats as compared to both Lyon Normotensive (LN) and Low Blood Pressure (LL) rats, except for a decrease in the C1 area of the medulla oblongata in 9 week-old animals.

[Effect of physical training by swimming on the arterial pressure, plasma and hypothalamo-post-hypophyseal vasopressin in genetically hypertensive rats of the Lyon strain]. / Effet de l'entraînement physique par la nage sur la pression artérielle, la vasopressine plasmatique et hypothalamo-post-hypophysaire chez de rat génétiquement hypertendu de la souche lyonnaise.

The effect of a 5-week swimming training on systolic blood pressure (PAS) and vasopressin (AVP) and Neurophysins (NpT) concentration in the blood and content in the pituitary and the hypothalamus was studied in Lyon genetically hypertensive rats [LH] and in their controls: the normotensive [LN] and low blood pressure [LL] rats belonging to the 28th generation. Nine female rats of each group were trained 5 days a week for 5 weeks, starting with 2 h a day, with a 15 min increase every day, up to 6 h a day. The PAS was measured using an indirect plethysmographic technique one time a week during the whole training session. At the end of the training, the rats were decapitated. AVP and NpT were measured in blood, pituitary and hypothalamus, by radioimmunoassay (RIA). Hematocrit as well as plasma Na+, K+, protein and osmotic content were also measured. Results show that the training did not affect any of the studied parameters: mainly, there was no decrease in PAS or plasma AVP level in the hypertensive rats compared to the normotensive ones. The only difference was a lower AVP content in the pituitary of LH rats compared to LN (p less than 0.01), which is difficult to interpret. Our results shed doubt on the efficiency of a swimming training on the evolution of hypertension in the Lyon rat model.

Selective reduction of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and increase of hypothalamic adrenaline levels in the Lyon strain of genetically hypertensive rats.

Catecholamine levels and turnover have been studied in 5 week old male genetically hypertensive (LH) and normotensive (LN) rats of the Sprague-Dawley Lyon strain. The results demonstrate increased hypothalamic adrenaline levels and a reduced adrenaline turnover in the dorsal midline of the medulla oblongata (DCMO) in the LH rats compared with LN control rats. The reduction of adrenaline turnover in the DCMO may contribute to the development of spontaneous hypertension.

[Bartter's disease associated with hypercorticism, phosphate and magnesium deficiencies and familial renal tubular disease]. / Un syndrome de bartter associant un hypercortisolisme, un diabete phosphore et magnesien et une tubulopathie d'origine familiale

A new case of Bartter's syndrome is described. There is a context of other cases of familial renal tubular disease with a sex-linked heredity. In this case, the Bartter's syndrome is associated with magnesium deficiency and hypomagnesemia, with a ricket and severe phosphate deficiency, and finally with an hypercorticism. The basal secretion rate of cortisol agree with a Cushing's syndrome. This hypercorticism is corrected by aminogluthetimide. The influence of the hyperreninism on the hypercorticism is discussed.