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J Sassard

Publications and source records attributed to J Sassard.

At least 163 records · Page 9Linked to original sources

[Dietary calcium and arterial hypertension in the rat].

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.

Animals↗

Urinary 6-ketoprostaglandin F1 alpha in genetically hypertensive rats of the Lyon strain.

In order to assess the pathophysiological role of renal prostacyclin in genetic hypertension, the urinary excretion of its main stable metabolite, 6-ketoprostaglandin F1 alpha, was followed in 12 hypertensive, normotensive and low blood pressure female rats of the Lyon strains at the ages of 5, 9, 21, 32 and 45 weeks. The urinary excretion of 6-ketoprostaglandin F1 alpha, which progressively decreased in the three strains between 5 and 21 weeks of age, was found to be increased in 5- and 9-week-old hypertensive rats and it was reduced in 5-week-old low blood pressure rats, compared with age-matched normotensive controls. The urinary 6-ketoprostaglandin F1 alpha was found to be significantly related to the systolic blood pressure in 5- and 9-week-old rats of the three strains (r = 0.42; n = 71; P less than 0.001). These results exclude a primary role in the development of hypertension for a genetically determined defect in the renal biosynthesis of prostacyclin in the spontaneous hypertensive rat of the Lyon strain.

6-Ketoprostaglandin F1 alpha↗

Central and peripheral catecholamine synthesizing enzymes during the development of two-kidney, one clip hypertension in rats.

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.

Adrenal Medulla↗

[Computerized analysis of cardiovascular activity in the conscious unrestrained rat. Application to the study of a new antihypertensive agent].

A more precise knowledge of cardiovascular activity in rats needs its direct recording for long periods of time, in conscious unrestrained animals. A system has been developed, which allows direct recording of blood pressure (BP) in freely moving rats, by means of a floating catheter chronically inserted in the abdominal aorta, connected to a rotating swivel, and then to a pressure transducer. A mini-computer performs on-line processing of BP curves, and stores the values of 5 cardiovascular parameters on hard disk: systolic, diastolic and mean arterial pressures, heart rate and dp/dt max. Off line processing allows graphic and statistical analysis of the data. Simultaneously recording from two rats is very useful in pharmacology because a treated animal and a control one are studied at the same time and in the same conditions. This methodology was used to evaluate the effects of a chronic treatment (2 mg/kg, ip, during 8 days) and of single injections (0.5 and 3 mg/kg, iv) of a new antihypertensive substance, CM 40441a, in 15 W old males SHR.

Adrenergic beta-Antagonists↗

Effects of chronic beta-blocker treatment on catecholamine levels in spontaneously hypertensive rats.

In the present work the effects of a 55-day oral treatment with two beta-blocking agents (propranolol 40 mg/kg per day and S 2395 20 mg/kg per day) on the catecholamine (CA) content of central and peripheral structures were studied in spontaneously hypertensive rats (SHR). The concentrations of dopamine (DA), noradrenaline (NA) and adrenaline (A) in different structures dissected out from treated and control SHR were measured by a radioenzymatic method. At the peripheral level, no change in the concentration of NA (in the heart) or A (in the adrenal medulla) was observed. Propranolol increased the DA concentration in the C1 and C2 regions of the medulla oblongata and S 2395 increased the DA concentration only in the C2 region. In these two areas, the NA and A levels were unchanged. Both propranolol and S 2395 increased the DA, NA and A content in the locus coeruleus and in the anterior hypothalamus. On the contrary, there was no modification in the posterior hypothalamus. The anatomical specificity of these alterations of the CA levels suggests that they could be related to a specific action of beta-blockers on central catecholaminergic structures in SHR which might be linked to the antihypertensive effects of these drugs.

Adrenergic beta-Antagonists↗

Chronopharmacokinetic study of a prolonged release form of indomethacin.

The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma O-desmethyl indomethacin was significantly higher after administration of indomethacin at 20 h than at 8 or 12 h. It is concluded that the pharmacokinetics of the oral prolonged-release form of indomethacin exhibited chronobiological variation. The data are in accordance with clinical studies which suggest that it might be worthwhile to administer this formulation of indomethacin at 20 h.

Adult↗

[Structural modification of the erythrocyte membrane in genetically hypertensive rats of the Lyon strain].

The rotation activation energy of 16 nitroxystearate spin label inserted in the erythrocyte membrane of genetically hypertensive (LH) and normotensive (LN) Rats from the Lyon strain was measured as a function of the age. This parameter was found significantly increased in the LH Rats compared to their normotensive LN controls. The same phenomenon has been observed previously in the Japanese spontaneously hypertensive Rats.

Animals↗

[Comparative effects of an alpha 1 and beta 1-2 blocker (labetalol) and a beta-1 blocker (atenolol) in the hypertensive patient].

The effects of a single oral dose and of an 8 week treatment with labetalol--an alpha 1- and beta 1-2-adrenoceptor blocking agent--and with atenolol--a beta 1-adrenoceptor blocking agent--were compared in 52 hypertensives. A single oral dose of atenolol induced a marked bradycardia without decrease in blood pressure. On the contrary labetalol lowered blood pressure but not resting heart rate. After an 8 week treatment both drugs exhibited a similar antihypertensive effect. However labetalol did not decrease heart rate and plasma renin activity as markedly as atenolol did. It was concluded that the alpha 1 blocking properties of labetalol were of importance in the development of the antihypertensive properties that this drug exhibits after a single or multiple administrations.

Adult↗

A new technique for the measurement of urinary 6-keto-prostaglandin F1 alpha: normal values in adults.

A new sensitive and specific radioimmunoassay for measurement of urinary 6-keto-prostaglandin F1 alpha is described. In this technique, 6-keto-prostaglandin F1 alpha was first extracted and separated from prostaglandins F2 alpha, F1 alpha, E2, E1, A2 and A1 by using an original high performance liquid chromatographic method with an overall recovery of 74.4 +/- 0.9%. The radioimmunoassay used a highly specific antibody raised in the rabbit. The sensitivity of the method was 1.8 pg. Between-assay reproducibility was at 7.7%. As previously reported for prostaglandins E and F alpha, the urinary excretion of 6-keto-prostaglandin F1 alpha, measured in 28 healthy adult subjects, was found to be significantly (p less than 0.001) higher in men (319 +/- 21 ng/24 h) than in women (190 +/- 14 ng/24 h). The chromatographic separation method described here could also be applied to the radioimmunoassay of other primary prostaglandins.

6-Ketoprostaglandin F1 alpha↗

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.

Animals↗

Nalidixic acid kinetics in renal insufficiency.

1 A pharmacokinetic study of nalidixic acid (NA) and metabolites was carried out in 23 patients with differing renal function so as to determine the influence of renal insufficiency on the excretion and biotransformation rate of this antibacterial agent. Plasma and urine concentration of NA and of its 7-hydroxy (HNA) and 7-carboxy (CNA) derivatives were measured after a single oral administration. 2 Renal insufficiency did not markedly affect the renal clearance of NA while it significantly decreased the elimination rate of HNA, a compound which largely excreted into the urine. 3 Interestingly, CNA which could never be detected in the plasma of patients with normal renal function appeared in that of patients with renal insufficiency. Plasma concentrations of CNA and creatinine were positively related, and the amount of urinary CNA increased with the renal impairment. 4 These results suggest that HNA can still be biotransformed into CNA by the impaired kidney. Since CNA cannot be easily excreted in the urine of patients with renal insufficiency it is hypothesized that this compound back diffuses into the plasma. 5 Finally, the study of the urinary concentrations of NA and metabolites shows that a standard NA dosage can be used, at least in patients with mild renal insufficiency.

Adult↗

Pharmacokinetics of intravenous camazepam in dogs.

Free plasma concentrations were studied after i.v. administration of three different doses (2.5, 5, 7.5 mg/kg respectively) of 3-N,N-dimethylcarbamoyloxy-7-chloro-5-phenyl-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (camazepam) to three healthy male mongrel dogs. Total plasma concentration was measured by a specific gas-liquid chromatography technique. The protein binding of camazepam in dog plasma was studied by using the equilibrium dialysis method and found to vary from 88.5 to 76.7% when the total drug concentration increased from 8 ng/ml to 8 micrograms/ml. For the subsequent pharmacokinetic analysis the calculated free camazepam plasma concentrations were used. The superposition principle was applied to each dog demonstrating that a linear pharmacokinetic model was applicable. Computer analysis showed that the pharmacokinetics of camazepam could be conveniently described by a three-compartment model assuming that the drug elimination occurred from the central compartment exclusively. The half-life of the terminal elimination phase ranged from 6.4 to 10.5 h, a finding which might suggest that camazepam could exhibit long-lasting effects.

Animals↗