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Biomedical subjects

J Sassard

Publications and source records attributed to J Sassard.

At least 181 records · Page 10Linked to original sources

[Vascular reactivity in young genetically hypertensive rats of the Lyons strain].

The vascular sensitivity to noradrenaline (NA), phenylephrine (PE) and angiotensin II (AII) has been studied in 8 week-old male rats of the genetically hypertensive (LH) and normotensive (LN) Lyon strains. Vascular sensitivity was obtained from the blood pressure response-curves observed in urethane anesthetized rats having received ganglioplegics and atropine. A cocaine pretreatment allowed to assess the influence of a reuptake blockade on the responses to NA. The vascular sensitivity of NA, PE and AII was normal in LH rats, while the cocaine blocked reuptake process was less important in LH than in LN rats. When comparing these results to those, previously obtained on the activity of the sympathetic nervous system, it appeared that: in the young prehypertensive LH rat an increased sympathetic activity was associated with a normal vascular reactivity to NA. On the contrary, in old LH rats, with established hypertension, the sympathetic activity returned to normal while a vascular hypersensitivity to NA developed. Therefore it is concluded that the overall efficacy of the sympathetic nervous system is increased at all stages of the development of genetic hypertension in the Lyon strain.

Angiotensin II↗

[The renin-angiotensin system and the sympathetic nervous system in essential hypertension].

In 112 patients with essential hypertension (HTA), free of any therapeutic and receiving the standard ward, a significant inverse relationship was found between age and plasma renin activity (PRA) and plasma aldosterone (PA), measured in the supine and upright position. Urinary epinephrine and norepinephrine were not related with age. When dividing the patients in 4 different age groups, it appeared that those younger than 30 years exhibited a significantly higher PRA and PA values and a higher frequency of borderline hypertension (45 p. 100) than the older ones (12 p. 100). So as to determine the characteristics associated with borderline HTA, it was necessary to eliminate the influence of age. This was achieved by comparing two groups of carefully age-matched patients, one with borderline HTA and the other with stable HTA. The only significant difference found was a significantly more marked increase in PRA in response to orthostatism, in patients with borderline HTA. Since renin responses to an orthostatic stress are largely mediated by renal nerves, this result suggest that borderline HTA could be associated with an increased reactivity of the sympathetic nervous system.

Adult↗

Radioimmunoassay for urinary prostaglandins E and F alpha: normal values in different age groups.

A new radioimmunoassay for urinary prostaglandins E and F alpha is described which allows the extraction and chromatographic separation of urinary prostaglandins with an overall recovery of 80.5% and 89.3% for prostaglandins E2 and F2 alpha respectively. The antibodies raised in the rabbit could not distinguish prostaglandins of series 1 and 2 but were found highly specific towards their metabolites and other primary prostaglandins. The sensitivity of the assay developed was at 2.2 pg for prostaglandin E and 2pg for prostaglandin F alpha. This assay was applied to normal adults of both sexes; it was shown that the daily urinary excretion of prostaglandins F alpha and E was greater in men than in women. In children aged from 1 to 114 months, the urinary excretion of prostaglandins increased with age. This increase was more marked during the first two years of life and was significantly related to age.

Adult↗

Nalidixic acid kinetics after single and repeated oral doses.

The kinetics of nalidixic acid (NA) and its two metabolites, 7-hydroxynalidixic acid (HNA) and 7-carboxynalidixic acid (CNA) were studied after a single oral dose and after two doses a day for 7 days. Total unconjugated NA, HNA, and CNA concentrations in plasma and urine samples were assayed by a new high-pressure liquid chromatographic (HPLC) technique. NA was rapidly absorbed and hydroxylated to HNA. Both were rapidly excreted in urine with an apparent elimination half-life (t1/2) of 6 to 7 hr. CNA was never detected in the plasma, although it accounted for about 25% of total urinary NA and metabolites. No major sex-related differences in the kinetics and the metabolic pattern were observed. During the 7-day treatment there was no significant cumulation of NA and HNA. The study demonstrated that the concentration of the active compounds, unconjugated NA and HNA, was more than five times the minimum bacteria inhibiting concentration for 8 hr after drug and slightly above this concentration during the next 4 hr.

Adult↗

Urinary excretion of prostaglandins and electrolytes in developing children.

A longitudinal study of the urinary excretion of prostaglandins (PG's) E and Falpha was performed in 55 healthy children aged from 1 to 114 months. In addition, the urinary PG's and electrolytes were studied in 6 children with Bartter's syndrome before and after an oral treatment with indomethacin. In normal children, both urinary PGE and PGF alpha increased with age, more markedly before 24 months of age. During this period, a positive and significant correlation was found with the urinary osmolality (r = 0.61, N = 16, P less than 0.05 for PGE; r = 0.82, N = 16, P less than 0.001 for PGF alpha). At every age, the urinary PG's were related to the potassium excretion (r = 0.68, N = 55, P less than 0.001 for PGE; r = 0.65, N = 55, P less than 0.002 for PGFalpha) but not to the natriuresis. In children with Bartter's syndrome, the increased urinary excretion of PGE, PGFalpha and potassium when the natriuresis was either decreased or increased after treatment. These results suggest that the renal PG's might play a role in the control of potassium excretion by the kidney. In addition, the determination of normal values in different age groups appears necessary for an accurate interpretation of the urinary PG's.

Bartter Syndrome↗

Relationships between blood pressure and plasma renin, aldosterone and dopamine-beta--hydroxylase in the elderly. Studies in patients over 70 years of age.

Plasma renin activity (PRA), aldosterone (PA) and dopamine-beta-hydroxylase activity (DBH) were measured in 49 subjects over 70 years of age, selected for normal or high blood pressure level. By comparison with younger controls, elderly subjects exhibited lower supine or upright PRA, but similar PA and DBH. No relationship could be found between individual blood pressure, and PRA, PA or DBH. The data favor the view that the renin-angiotensin-aldosterone system does not play an important causative role in elderly hypertension. They also point to the necessity of age-matched controls when this system is being studied in elderly patients.

Aged↗

A longitudinal study of plasma renin activity during normal and preeclamptic pregnancy.

In 68 pregnant women, blood samples were obtained at 12, 20, 25, 29, 32 and 36 weeks. Plasma renin activity (PRA) was measured in 10 of them, who developed "pregnancy induced hypertension" ("PIH") and in 10 normal pregnant women, matched with the hypertensive patients for age, parity and body weight. Towards the end of pregnancy, PRA showed a tendency to increase in the "PIH" group, and to decrease in the control group. However, these variations were not statistically significant. There was no significant difference between the two groups, except for the last measurement, obtained at the 36th week of gestation. At this time, PRA was more elevated in the PIH group. We conclude that PRA measurements early in pregnancy are of no value in predicting if women are going to develop PIH.

Female↗

[Effects of labetalol, a new alpha- and beta-adrenoreceptor blocking drug, on arterial pressure, renal function and renin activity (author's transl)].

Labetalol, a blocker of alpha- and beta-adrenoreceptors, was tried on 45 patients with severe (29 cases) or mild to moderate (16 cases) hypertension. After an initial period of dosage adjustment and a 2 months treatment in effective doses, there was a significant fall in supine blood pressure from mean values of 207/132 to 170/106 mmHg. In 23 patients hypertension was controlled by labetalol alone in doses of 400 and 1800 mg per day. True failures were rare (16%). Digestive disorders and postural hypotension were the most frequently encountered side-effects; they obliged to discontinue treatment in 4 cases, but were compatible with it in 11 cases. In 22 patients the fall in BP was accompanied by a significant (p less than 0,001) decrease in plasma renin activity from 123 to 44 ng/l/min supine and from 144 to 83 ng/l/min standing. Studies of the renal function showed no changes during oral therapy. Following intravenous injection of 50 mg labetalol to 20 subjects, inulin and PAH clearances remained unaltered, and there was a significant, though transient (1 hour), decrease in chloride, sodium and phosphorus excretion. Effective in lowering blood pressure be used and well tolerated by the kidneys, labetalol can safely be used for the treatment of severe hypertension with organic renal involvement.

Adolescent↗

Determination of nalidixic acid and its two major metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography.

This paper describes a precise and sensitive method for analysis of nalidixic acid and its two major metabolites in plasma and urine following the oral administration of a therapeutic dose in humans. After addition of an internal standard (oxolinic acid), 1-ml samples of plasma or urine are extracted at acidic pH with chloroform. The extracts are purified by re-extraction with sodium hydroxide solution and then chloroform. The final extracts are evaporated to dryness, reconstituted in mobile phase and injected into a high-performance liquid chromatograph equipped with RP-8 column and UV detector operating at 254 nm. The limit of sensitivity of the method is lower than 0.5 micrograms/ml of plasma or urine for each compound. The applicability of the method to pharmacokinetic studies of nalidixic acid in humans is demonstrated.

Chromatography, High Pressure Liquid↗

Plasma renin activity, aldosterone and dopamine beta-hydroxylase activity as a function of age in normal children.

In 149 children between 6 days and 15 years of age, plasma renin activity (PRA) and aldosterone (PA) were measured by radioimmunoassay and plasma dopamine beta hydroxylase activity (DBH) by the method of Nagatsu. PRA and PA decreased with age from 496 +/- 119 ng/1/min for PRA and 643 +/- 158 pg/ml for PA in 6 to 30 day-old newborns to 37.8 +/- 4.7 ng/1/min for PRA and 43. 1+/- 8.3 ph/ml for PA in 9 to 15 year-old children. DBH increased with age from less than detection limit values (< 2 IU) in 6 day to 3 month-old newborns to 17.2 +/- 5.1 IU in 9 to 15 year-old children. In addition a significant relationship was found between PRA and PA (log PA = 0.99 log PRA -0.058, r = 0.732, n = 104, p < 0.001) and PRA and DBH (log DBH = -0.41 log PRA +1.62, r = 0.404, n = 80, p < 0.001). These results demonstrate the opposite evolution of the Renin-Angiotensin-Aldosterone System and of the sympathoadrenal system during development.

Adolescent↗

Abnormal net Na+ and K+ fluxes in erythrocytes of three varieties of genetically hypertensive rats.

Net Na+ and K+ fluxes were measured in Na+-loaded and K+-depleted erythrocytes of three varieties of genetically hypertensive rats. In Okamoto spontaneously hypertensive rats (4 and 10-12 weeks of age), Na+ extrusion was reduced as compared to normotensive controls (Wistar/Kyoto). Na+ extrusion was also reduced in the hypertension-prone substrain of the Hebrew University Sabra rats as compared to the Na+-resistant substrain. K+ fluxes were similar in both groups. In both Okamoto spontaneously hypertensive rats and the hypertension-prone substrain, hypertension was severe and developed rapidly. In the Lyon spontaneously hypertensive rats, in which the blood pressure elevation is less severe than in other genetically hypertensive rats, erythrocyte net Na+ extrusion was the same as in normotensive controls, but net K+ gain was slightly increased. These erythrocyte abnormalities, observed in three varieties of genetically transmitted hypertension of the rat, are in several aspects similar to those previously described in accelerated and benign human essential hypertension. Erythrocyte Na+ and K+ net flux alterations may thus represent biochemical markers of primary hypertension.

Animals↗

Urinary excretion of catecholamines and metabolites in the Lyon strain of genetic hypertensive rats.

Urinary catecholamines (Norepinephrine : NE, Epinephrine : E) methoxylated amines (Metanephrine : MN, Normetanephrine : NMN) and 3-methoxy-4-hydroxyphenylglycol (MHPG) have been studied in the Lyon hypertensive strain of rats (LHS) and their normotensive controls (LNS) at three ages (5, 9 and 21 weeks) characteristic of the development of hypertension. In 5-week-old rats, increased excretion of E, MN, NMN and early elevation of the ratio E/E+NE were observed, thus suggesting a sympatho-adrenal hyperactivity, with accelerated maturation of E secretion. At adult age, the excretion of most adrenergic metabolites was similar in the two strains of rats. However, the data from adult LHS are difficult to interpret because of a potential renal impairment at this age. Furthermore, there was a positive correlation between systolic blood pressure and urinary catecholamines at 5 weeks and 9 weeks of age but not at 21 weeks. It is suggested that the early sympathoadrenal hyperactivity, which disappears with age, may be related to the onset of hypertension in the Lyon strain of hypertensive rats.

Adrenal Glands↗

[Renin-angiotensin system. Physiological importance. Methods and study in humans (author's transl)].

After a brief review of the biochemistry of the renin-angiotensin system (R. A. S.) components and of their pharmacological inhibitors, the authors describe the main biological effects of angiotensins. A particular emphasis is given to the synergistic effects of the sympathetic nervous system and of the R. A. S., and their major influence on the regulation of hydromineral metabolism and blood pressure. The methods developed for the study of R. A. S. are critically described. Finally, the most important clinical indications of the study of R. A. S. activity are given, and a special attention is paid to the conditions in which such a study must be developed in humans.

Adolescent↗