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Biomedical subjects

J Sassard

Publications and source records attributed to J Sassard.

At least 145 records · Page 8Linked to original sources
PubMed1986

Cardiac and renal hyperplasia in newborn genetically hypertensive rats.

Newborn spontaneously hypertensive rats (SHR), compared with Wistar-Kyoto (WKY) controls, usually show cardiac and renal hyperplasia. To determine whether these anomalies are common to genetically hypertensive rats, we examined newborn rats from models of essential hypertension (Kyoto, Montreal, Dunedin and Lyon strains of hypertensive rats), renal hypertension (Milan strain of hypertensive rats) and experimental hypertension [deoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats]. The hearts, kidneys and livers of these newborns were collected on site at various centres and sent to Montreal for protein and DNA determinations. The results showed that protein and DNA, corrected for body weight in models of essential hypertension, were increased in the heart and kidney, and normal or decreased in the liver at birth. This pattern differed in offspring of the Milan strain (renal hypertension) and of DOCA-salt hypertensive animals (experimental hypertension). Since cardiac and renal hyperplasia associated with the hypertensive trait in four different genetic models of spontaneous hypertension was distinct from that observed in renal and experimental hypertension, it is conceivable that a specific cardiovascular growth pattern is a reflection not of a simple linkage or consequence, but of a causal association with spontaneous hypertension.

Animals↗
PubMed1986

[Urinary excretion of thromboxane B2 in the genetically hypertensive rat of the Lyons strain].

In order to assess the pathophysiological role of the renal Thromboxane (Tx)A2 in genetic hypertension, the urinary excretion of its stable metabolite: the TxB2 was followed in groups of 12 hypertensive (LH), normotensive (LN) and low blood pressure (LL) female rats of the Lyon strains at the ages of 5, 9, 21 and 32 weeks. In the 3 strains studied, the urinary TxB2 excretion markedly decreased between 5 and 9 weeks of age and did change thereafter. In addition, 5 and 9 weeks old rats exhibited an increased urinary TxB2 output compared to LN and LL controls. Since TxA2 is a potent vasoconstrictor, it seems likely to hypothesize that the early increase observed in the renal TxA2 biosynthesis could be one of the primary events occurring during the development of hypertension in this rat model.

Aging↗
PubMed1986

Comparison of various genetic hypertensive rat strains.

Comparative studies on nine genetic hypertensive rat strains [two stroke-prone spontaneously hypertensive rats (SHRSP) and Dahl salt-sensitive (DS) strains, and one strain each of spontaneously hypertensive rats (SHR), Lyon hypertensive rats (LH), Milan hypertensive strain (MHS), genetically hypertensive rats (GH) and Sabra hypertensive rats (SBH)] and their respective controls [two Dahl salt-resistent (DR) strains and one strain each of Wistar-Kyoto rats (WKY), Lyon normotensive rats (LN); Lyon low blood pressure rats (LL), Milan normotensive strain (MNS), genetically normotensive rats (GN) and Sabra normotensive rats (SBN) and their original strain, Sabra rats (SB)], in groups consisting of 6-10 males from each strain, were carried out at 10-12 weeks of age under the same experimental conditions. After checking the developmental course of blood pressure and changes in body weight, they were killed at 12 weeks of age for blood analysis and organ-weight examinations. The SHRSP and SHR showed markedly higher blood pressure levels and earlier blood pressure rises in comparison with other hypertensive strains, although they had higher blood pressure than their respective controls. Among various organ weights examined, all hypertensive strains commonly showed increases in left ventricular weight in proportion to blood pressure rises. Kidney weights were significantly decreased only in MHS compared with MNS, while they were either unchanged or significantly greater in other hypertensive strains. Weights of adrenal glands were greater in the two strains of DS and in LH than in their respective control strains. These comparative data indicate possible differences in the pathogenic mechanism involved in these genetic hypertensive rat strains.

Animals↗
PubMed1986

Effect of swim training on systolic blood pressure, vasopressin and total neurophysins in the Lyon hypertensive rat.

This study reports the effects of 5 weeks of swim training on systolic blood pressure, body weight, plasma and brain vasopressin and total neurophysins in the Lyon genetically hypertensive (LH) rat and in their normotensive (LN) and low blood pressure (LL) controls. Swimming was unable to influence any studied parameters. These results shed doubt on the efficiency of this model of training on the evolution of hypertension in the LH rats.

Animals↗
PubMed1986

Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

Genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains have been simultaneously selected according to their systolic blood pressure (SBP). SBP and immunological parameters were investigated in 5 week-old rats. SBP reached 99 +/- 2 mmHg in LL, 108 +/- 2 mmHg in LN and 122 +/- 4 mmHg in LH. White blood cell and lymphocyte counts, thymus and spleen histology, percentages of T cells and subsets of T cells in these organs were not modified by genetic hypertension. The blastogenic responses to mitogens (Con A and PWM) of the LH rat thymocytes were similar to those observed in LN or LL rats. By contrast, the proliferative response of splenocytes to PWM was positively correlated (r = 0.93) with SBP level. In additional experiments we demonstrated that, besides the immune defect induced by neonatal thymectomy, the removal of the thymus at birth prevented the spontaneous increase of SBP in LH strains (102 +/- 2 mmHg instead of 122 +/- 4 mmHg), while only a slight decrease or no alteration was seen in LN and LL thymectomized rats. This antihypertensive effect tended to maintain SBP at a common level in the 3 strains. These results suggest that the thymus may be involved in the development of genetic hypertension.

Animals↗
PubMed1985

Measurement of urinary catecholamines and their catechol metabolites and precursor by liquid chromatography with column-switching and on-line fluorimetric and electrochemical detection.

A new method is described for the determination of catecholamines and their precursor (3,4-dihydroxyphenylalanine), and separately of their catechol metabolites (3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethylene glycol and 3,4-dihydroxyphenylethanol) in urine. After a two-step pretreatment involving ethyl acetate extraction and adsorption onto alumina, the separation is performed by ion-pair reversed-phase high-performance liquid chromatography. A column-switching system enables complete separation of the most polar compounds without increase in the total analysis time. The column eluates are monitored with both fluorimetric and amperometric detectors, the relative responses of which are used as an index of peak purity. Reference values for twelve healthy adults are given.

Adult↗
PubMed1985

Catecholamine concentrations in discrete brain nuclei and sympathetic tissues of genetically hypertensive mice.

Catecholamine concentrations were determined at central and peripheral level in high blood pressure (HBP), low blood pressure (LBP) and random bred (RB) mice. In HBP mice compared to LBP, the noradrenaline concentration was lower in the locus coeruleus, medullary A1-C1 and A2-C2 areas, thoracic spinal cord, posteroventral hypothalamus and nucleus hypothalamicus anterior, while dopamine concentration was decreased in the striatum. Adrenal catecholamine levels were higher in both HBP and LBP compared to RB mice.

Adrenal Medulla↗
PubMed1985

Brain, spinal cord and adrenal catecholamine concentrations in neonate rats of the Lyon hypertensive strain.

The catecholamine concentrations were determined in brain parts, spinal cord and adrenals of neonate hypertensive rats of the Lyon strain (LH), compared to normotensive (LN) and low-blood-pressure (LL) control rats. In adrenals of LH rats, noradrenaline and adrenaline concentrations are increased, and 3,4-dihydroxyphenylacetic acid (DOPAC) concentration decreased. At the central level, the DOPAC concentration and the ratio DOPAC/dopamine are decreased in the mesencephalon and the forebrain of LH rats. These results suggest that neonate LH rats exhibit a decreased activity in central dopaminergic neurons, and an enhanced maturation of the adrenals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

High-performance liquid chromatographic determination of cicletanide, a new diuretic, in plasma, red blood cells, urine and saliva.

A sensitive, selective and easy to use high-performance liquid chromatographic method for the determination of cicletanide, a new diuretic, in plasma, red blood cells, urine and saliva is described. After extraction of cicletanide together with an internal standard with diethyl ether, or diethyl ether-n-hexane (20:80) for urine, the sample extracts are chromatographed with water-methanol-acetic acid (50:50:0.3) as eluent on to a Nucleosil C18 column. Both compounds are detected by their ultraviolet absorption at 280 nm. The calibration graph was linear between 0.2 and 20 micrograms/ml for plasma and between 0.2 and 5 micrograms/ml for the other biological fluids. The sensitivity limit was 20 ng/ml for plasma, red blood cells and saliva and 30 ng/ml for urine. The coefficients of variation of the between-day assays did not exceed 4.6% in plasma, 8.3% in red blood cells, 7.8% in urine and 4.2% in saliva for the lowest concentrations studied. The application of the method to a pharmacokinetic study of cicletanide after a single oral therapeutic dose in humans is reported.

Chromatography, High Pressure Liquid↗
PubMed1985

Influence of renal failure on the kinetics of zimeldine and norzimelidine.

The kinetics of zimeldine (Z) and its demethylated metabolite, norzimelidine (NZ), were determined after administration of a single 200 mg oral dose of Z to 6 healthy volunteers (Group I), and to patients with mild (Group II) and severe renal failure (Group III). Z and NZ concentrations were assayed by HPLC in serial plasma and urine samples over 6 days following the dose. In Group I Z was rapidly absorbed and metabolized into NZ, and then the plasma concentrations declined with apparent elimination half-lives of 8.4 h and 24.9 h for Z and NZ respectively, whilst the renal clearance of both compounds was low, Z 15.7 ml/min and NZ 33.0 ml/min. The plasma level of Z differed little between Groups I and III, but the area under the curve was significantly higher in Group III than in Group I subjects (AUC0-144 = 17.3 and 6.8 mumol X l-1 X h, respectively). Severe renal failure did not affect the peak plasma concentration of NZ but it did significantly increase peak time, apparent elimination half-life, and the area under the plasma concentration curve. A significant inverse relationship was found between renal clearance of NZ and plasma creatinine. Since NZ is as pharmacologically potent as Z, the results suggest that the dose of Z should be reduced in patients with severe renal insufficiency.

Adult↗
PubMed1985

Pharmacokinetics of penbutolol and its metabolites in renal insufficiency.

The pharmacokinetics of penbutolol, its 4-hydroxylated metabolite and of their conjugates was studied in hypertensive patients with various degrees of renal impairment. A single oral dose of penbutolol 40 mg, was rapidly absorbed after a lag-time of 0.34 h. Its plasma concentration reached a maximum after 0.84 h and then declined bi-exponentially, with an apparent elimination half-life of 21.8 h. The hydroxylation of penbutolol was negligible and conjugation was of major importance for its elimination. Consequently, the kinetics of unchanged penbutolol were not altered by renal impairment. The 48 h-urinary excretion of penbutolol and its metabolites reached 13-14% of the administered dose, which is consistent with extensive metabolism of the drug. After treatment for 30 days with penbutolol 40 mg/d there was no accumulation of the parent drug but the concentration of its conjugates was increased. It is concluded that the dose of penbutolol need not be changed in patients with mild renal insufficiency, 4-hydroxypenbutolol is unlikely to participate in the anti-hypertensive effect of the drug, due to its low concentrations, and biotransformation of penbutolol may be enhanced during chronic treatment.

Adult↗
PubMed1985

Computer analysis of intraarterially recorded blood pressure in conscious unrestrained rats.

A precise knowledge of cardiovascular activity and its pharmacological modifications in the conscious unrestrained animal requires intraarterial blood pressure recording for long periods of time. For that purpose, a technique was developed involving chronic catheterization of the rat abdominal aorta and the use of a computer system to perform the digitization of the blood pressure signal and the on-line calculation of five cardiovascular parameters. By means of duplexing, two rats (one treated and one control) can be studied simultaneously. Off-line processing is devoted to the graphic treatment and statistical analysis of the data. The effects of a single intravenous administration of dihydralazine are presented in order to show the usefulness of the technique.

Animals↗
PubMed1985

A new radioimmunoassay for urinary thromboxane B2 with prior purification by high performance liquid chromatography.

In order to assess the role of the renally formed thromboxane A2 in humans, a new radioimmunoassay was developed for the determination of the urinary excretion of thromboxane B2, the stable metabolite of thromboxane A2. Urines were extracted with ethylacetate and thromboxane B2 was separated from the other primary prostaglandins by a reversed phase high performance liquid chromatography using water, acetonitrile and acetic acid (71:29:0.1) as mobile phase with an overall recovery of 44.1% +/- 1.3 (n = 42). The radioimmunoassay, performed on the fraction containing thromboxane B2 used a sensitive (less than 1pg) and highly specific antibody (final dilution: 1/460 800) that we have raised in the rabbit. The coefficient of variation was found lower than 5% in the usable part of the standard curve and the inter-assay reproducibility was at 7.3%. The 24-hour urinary excretion of thromboxane B2 measured in 26 healthy adults established at 109 +/- 12.9 ng/24h in men and at 99.5 +/- 9.2 ng/24 h in women. Therefore, it differed from that of the other prostaglandins by lower values devoid of sex-related differences.

Adult↗
PubMed1985

Computer analysis of cardiovascular activity in conscious unrestrained hypertensive rats of the Lyon strain.

A new computerized technique was developed for the continuous analysis of intra arterially recorded blood pressure (BP) curve in freely moving rats during long periods of time. For each cardiac cycle 5 parameters were calculated on-line and stored. Off-line processing allowed graphical display and statistical analysis. This technique demonstrated that 21 week-old genetically hypertensive rats from the Lyon strain (LH) exhibited higher and more variable BP and dp/dt max. with a lower heart rate than normotensive (LN) and low blood pressure (LL) controls. LL rats differed from LN by a slightly higher systolic and a lower diastolic BP.

Animals↗
PubMed1985

Cardiovascular effects of S 9490-3, a new converting enzyme inhibitor: a computerized study in conscious spontaneously hypertensive rats.

The acute cardiovascular effects of S 9490-3, a new angiotensin converting enzyme (ACE) inhibitor, were studied by means of a computerized analysis of the intra-aortic blood pressure (BP), recorded continuously for 48 h in conscious, unrestrained, adult spontaneously hypertensive rats (SHR). The first 24-h recording period was used as a control. On the second day, the rats received a single intravenous (i.v.) injection of S 9490-3 (0.2 mg/kg) at 11 a.m. followed by another 2 mg/kg i.v. injection at 3 p.m. Cardiovascular activity was studied up to 8 a.m. the next day. No significant cardiovascular effects appeared after the 0.2 mg/kg dose, whereas the 2 mg/kg dose induced a rapid fall in systolic and diastolic BP, which remained significant for about 11 h. This BP decrease was not associated with any elevation in heart rate, but with a short lasting increase in dP/dt max. These results are in good agreement with those already obtained with S 9490-3 in various experimental conditions. They suggest that long-term recordings of intra-arterial BP in freely moving rats is of value in the study of drugs which act on the cardiovascular system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

[Effect of physical training by swimming on the arterial pressure, plasma and hypothalamo-post-hypophyseal vasopressin in genetically hypertensive rats of the Lyon strain].

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.

Animals↗
PubMed1985

[Central and peripheral catecholamines in the genetically hypertensive mouse].

The aim of this work was to assess if biochemical alterations are present in catecholaminergic neurons of genetically hypertensive mice (HBP strain) compared to genetically hypotensive mice (LBP strain), as well as to mice of the population (R) from which HBP and LBP strains have been selected. For that purpose, dopamine (DA), noradrenaline (NA) and adrenaline (A) concentrations were determined by high performance liquid chromatography with electrochemical detection, in peripheral structures and brain nuclei of adult male mice from these three strains. In the adrenal medulla of HBP mice, DA, NA and A concentrations are increased when compared to R, but not to LBP mice. In the superior cervical ganglia of HBP mice, the NA concentration is decreased when compared to LBP, but increased when compared to R mice. At the central level, the NA concentration is decreased in HBP mice when compared to LBP, but not significantly changed when compared to R mice, in the following regions: locus coeruleus (-39 p. 100, p less than 0.001), A1-C1 (-17 p. 100, p less than 0.001) and A2-C2 (-19 p. 100, p less than 0.001) areas of the medulla oblongata, thoracic spinal cord (-26 p. 100, p less than 0.01), posteroventral hypothalamus (-18 p. 100, p less than 0.01) and nucleus hypothalamicus anterior (-14 p. 100, p less than 0.01). In the nucleus periventricularis, NA concentration of HBP mice is not changed when compared to both LBP and R animals. Finally, in the caudate nucleus of HBP mice, the DA concentration is decreased when compared to both R and LBP mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗