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Biomedical subjects

J Sassard

Publications and source records attributed to J Sassard.

At least 109 records · Page 6Linked to original sources
PubMed1989

Atrial natriuretic peptide and urinary prostaglandins in man.

1. In order to assess the effects of atrial natriuretic factor on the renal biosynthesis of prostaglandins (PG), the urinary excretion of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (Tx)B2 were followed in eight salt-loaded healthy volunteers infused for 2 h with a non hypotensive dose of human atrial natriuretic peptide (hANP, 0.7 nmol min-1). 2. Within 1 h, hANP, infusion produced a marked increase in the urinary PG output, especially of PGE2 and 6-keto-PGF1 alpha (188 +/- 21% and 202 +/- 24% of the pre-infusion values respectively), followed by a significant decrease during the recovery period. 3. No correlations could be uncovered between the urinary excretion of sodium and that of any of the PGs. In contrast, during the infusion of hANP, the urinary output of PGE2 and of 6-keto-PGF1 alpha was found positively related to the urinary flow rate (r = 0.42; P less than 0.05; n = 32 and r = 0.43; P less than 0.05; n = 32 respectively) as well as during the recovery period (r = 0.66, P less than 0.001; n = 32 and r = 0.55; P less than 0.01; n = 32 respectively). 4. It was concluded that, in man, infusion of a non hypotensive dose of hANP is followed by a rise in urinary PG excretion presumably reflecting enhanced renal PG biosynthesis. This increased urinary PG excretion does not seem to be involved in the natriuretic action of hANP but might participate to its diuretic effect.

Adult↗
PubMed1989

The influence of renal insufficiency and haemodialysis on the kinetics of ciprofibrate.

1. The kinetics of the hypolipidaemic drug, ciprofibrate, were studied after a single oral dose (100 mg) in subjects with normal renal function (n = 6), patients with mild (n = 6) and severe (n = 6) renal insufficiency as well as in haemodialysed patients (n = 5). 2. Under fasting conditions, ciprofibrate, was absorbed rapidly in subjects with normal renal function, and its apparent elimination half-life was approximately 81 h. Both renal clearance (0.15 ml min-1) and cumulative renal excretion (less than 7% of the administered dose) were low. 3. Mild renal insufficiency did not alter the pharmacokinetics of ciprofibrate, but severe renal impairment significantly reduced both its renal clearance and cumulative urinary excretion and increased the apparent elimination half-life. 4. A 5 h haemodialysis session did not lower the plasma concentrations of ciprofibrate. 5. It is concluded that, from a pharmacokinetic point of view, a reduction in the dosage of ciprofibrate should be considered in patients with a glomerular filtration rate below 30 ml min-1/1.73 m2.

Adult↗
PubMed1989

Cardiovascular effects of rilmenidine, a new alpha 2-adrenoceptor agonist, and clonidine in conscious spontaneously hypertensive rats.

1. The acute and chronic effects of rilmenidine, a partial agonist of alpha 1- and alpha 2-adrenoceptors with antihypertensive properties, were compared to those of clonidine on blood pressure (BP), heart rate (HR) and the urinary excretion of catecholamines, which was used as an index of sympathetic activity. 2. As these drugs are known to interfere centrally and peripherally with the sympathetic nervous system, long-term arterial blood pressure recordings in freely moving unstressed adult spontaneously hypertensive rats (SHR) were used. 3. Acute i.v. administrations of rilmenidine (0.3 mg/kg at 1200 h, 1.2 mg/kg at 1700 and 2200 h) and clonidine (12 micrograms/kg at 1200 h, 50 micrograms/kg at 1700 and 2200 h) induced short-lasting increases in BP associated with a decrease in HR, which were followed by prolonged, dose-dependent decreases in BP without bradycardia. The pressor effect was less marked and the associated bradycardia was more marked in active SHR with physiologically high sympathetic activity than in resting SHR. 4. A 12-day oral treatment with rilmenidine (6.0 mg/kg daily) or clonidine (150 micrograms/kg daily) induced moderate decreases in BP without change in HR. Rilmenidine but not clonidine decreased normetanephrine (NMN) excretion in active but not in resting SHR. 5. Finally, during the 24 h following the cessation of the treatments, BP returned to normal, without significantly exceeding that of untreated controls. However, upswings in BP or HR were observed, more markedly and frequently after clonidine than after rilmenidine. 6. In conclusion the effects of alpha 2-adrenoceptor agonists appear to be influenced by the pre-existing sympathetic tone. The general agreement between these data and those observed in patients demonstrates that the use of conscious unstressed animals is of value to determine the cardiovascular effects of drugs which act on the sympathetic nervous system.

Administration, Oral↗
PubMed1989

Evolution with age of baroreflex sensitivity and its autonomic nervous components in conscious hypertensive rats of the Lyon strain.

1. Cardiac baroreflex sensitivity (BRS) and its sympathetic and vagal components were studied after atropine and propranolol administrations in conscious genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strain at 5, 9, 13 and 70 weeks of age. 2. LH rats older than 9 weeks exhibit a lower BRS than age-matched LN and LL controls. 3. The vagal component of cardiac baroreflex is predominant. In LN rats, this component increases up to 9 weeks of age. 4. The sympathetic component of cardiac baroreflex is small and identical in the three strains and does not alter with age. 5. Thus, in normotensive rats, the increase in BRS during maturation reflects mainly the vagal component. The development of hypertension prevents this physiological increase in the sensitivity of the vagal component of cardiac baroreflex leading to a reduced BRS.

Aging↗
PubMed1989

Steroids during development of genetic hypertension in rats of Lyon strain.

The urinary excretion and the plasma concentration of deoxycorticosterone (DOC), corticosterone, 18-hydroxy-DOC (18-OH-DOC), aldosterone, and 19-nor-DOC were measured by specific radioimmunoassays in genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains at two ages that characterize the development of their systolic blood pressure (SBP). When compared with both LN and LL controls, 5-wk-old LH rats exhibited an increased urinary DOC and decreased urinary corticosterone excretions, which were significantly related to the SBP level (r' = 0.618 and -0.520; n = 23; P less than 0.01 for DOC and corticosterone, respectively). In addition, the adrenal synthesis of LH rats was found to rely on an increased 18-hydroxylase activity as indicated by elevated urinary 18-OH-DOC/corticosterone and aldosterone/corticosterone associated with a lower 11-beta-hydroxylase activity shown by the decreased urinary corticosterone/DOC. Twenty-wk-old LH rats with fully developed hypertension exhibited normal urinary excretion of steroids and a decrease in plasma DOC concentration, which negatively correlated with the SBP level (r' = -0.574; n = 25; P less than 0.01). In conclusion, the present study demonstrates that in the Lyon model of genetically hypertensive rats, compared with two genetically different control strains and maintained under physiological unstressed conditions, the development of hypertension is associated with an increased urinary excretion of DOC. After the full development of their hypertension, the mineralocorticoid synthesis in LH rats returns to normal or low levels which could, however, remain inappropriately high for their sodium body content.

Adrenal Cortex Hormones↗
PubMed1989

[Blood pressure lability in the sympathectomized rat].

Intra-aortic blood pressure (BP) was measured in conscious rats after early chronic destruction of the peripheral sympathetic nervous system (SNS) with guanethidine. In sympathectomized rats, the mean level of BP was not different from that of control rats but its variability was markedly increased. These results indicate that functional integrity of the SNS is of primary importance for the short-term control of BP but is not essential for its long-term maintenance.

Animals↗
PubMed1989

[The sympathetic and renin-angiotensin systems are complementary in blood pressure regulation].

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.

Animals↗
PubMed1988

Effects of DOCA-salt treatment on the urinary prostaglandins in Sabra rats.

To determine whether the increased renal synthesis of thromboxane (Tx)A2 found in genetically hypertensive rats also occurred in rats with a sodium-dependent form of hypertension, the urinary excretion of 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) and of TxB2 was measured by a sensitive and specific radioimmunoassay in hypertension-prone (SBH), -resistant (SBN) and unselected (SB) female rats of the Sabra strains. Rats of the three strains were studied before (9 weeks of age) and after five weeks of deoxycorticosterone (DOCA)-salt treatment. Before treatment, the urinary 6KPGF1 alpha did not differ among the three strains while a higher TxB2 excretion was seen in the SBN rats. After treatment, the urinary excretion of TxB2 increased significantly in SBH and SB but not in SBN rats, while the urinary 6KPGF1 alpha remained unchanged in SBH, increased moderately in SB and markedly in SBN controls. Consequently, DOCA-salt-induced changes in blood pressure and in urinary 6KPGF1 alpha observed in the three strains of rats were inversely related (r = -0.78; P less than 0.001). It is concluded that the high blood pressure developed after DOCA-salt treatment in SBH rats is more likely to depend upon a defect in the renal production of prostacyclin rather than upon an increased synthesis of thromboxane A2.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Aging↗
PubMed1988

Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.

1. The kinetics of a single oral dose (300 mg) of cicletanine a new antihypertensive drug with diuretic properties, and its effects on the urinary excretion of electrolytes and of the major stable metabolites of prostacyclin and thromboxane A2 were studied in patients with normal renal function (n = 6), mild (n = 9) and severe (n = 10) renal insufficiency. 2. In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0.4 ml min-1) and its cumulative renal excretion (0.85% of the administered dose), were low. Mild renal insufficiency did not significantly alter these parameters, while severe renal impairment reduced the renal clearance and the cumulative urinary excretion of cicletanine and increased its apparent elimination half-life (31 h). However the area under the plasma curve was not changed due to reduced plasma concentrations in these patients. 3. Cicletanine induced a rapid and marked (four fold as a mean) increase in the urinary excretion of water, sodium and potassium which lasted for 6 to 10 h, in subjects with normal renal function. Renal insufficiency did not alter the slope of the calculated plasma concentration-effects curves but reduced the maximum effect observed for water, sodium and potassium. 4. A single oral dose of cicletanine did not change the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in the three groups of patients studied, the basal values of which being found to be closely related to the creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strain. Sham-operated animals served as controls. 2. Neonatal thymectomy prevented the spontaneous increase of SBP in LH rats while it slightly decreased the SBP of LN and did not change that of LL rats. 3. Five week old sham-operated LH rats exhibited an increased urinary excretion of DOC and a decreased excretion of B compared with both LN and LL controls. Thymectomy did not alter the urinary excretion of adrenal steroids in LN and LL rats. The urinary excretion of B was markedly enhanced in thymectomized LH rats whereas that of DOC remained unmodified. 4. These data suggested that the thymus could be involved in the development of hypertension in LH rats. 5. The antihypertensive effect of thymectomy did not seem to be mediated by a decreased mineralocorticoid production in the genetically hypertensive rat of the Lyon strain.

Aldosterone↗
PubMed1988

Cardiovascular response to emotional stress and spontaneous blood pressure variability in genetically hypertensive rats of the Lyon strain.

1. Intra-aortic blood pressure (BP) was continuously recorded in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of the Lyon strains under basal conditions and during aversive stimulation (a jet of air for 20 min). Rats were studied when 5 and 14 weeks old. 2. The 24 h standard deviation (i.e., variability) of diastolic BP was significantly greater in LH rats of both ages than in LN and LL control rats. 3. In response to the stressor, LH rats showed larger increases in BP than age-matched controls. 4. The BP variability was related to the BP responses to stress in the whole series of rats. 5. It is concluded that the spontaneous BP variability and the BP responses to an experimental stressor rely upon a common regulatory mechanism in rats and that an increased lability of diastolic BP is a primary characteristic of Lyon hypertensive rats.

Aging↗
PubMed1988

Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats.

1. The acute cardiovascular effects of PY 108-068 and PN 200-110 were studied by means of a computerized analysis of the intra-aortic blood pressure (BP) recorded continuously for 26 h in conscious unrestrained spontaneously hypertensive rats. Both compounds were studied at three doses (50, 100 and 200 micrograms kg-1) and each dose was administered intravenously 5 times (09 h 00 min, 14 h 00 min, 19 h 00 min, 24 h 00 min and 09 h 00 min). Baroreflex sensitivity was measured 1 h following the last injection. 2. The two compounds were found to induce rapid (3 min) and dose-dependent falls in BP. After the first administration, these decreases reached -20% and -35% for systolic BP (SBP) and diastolic BP (DBP) respectively with PY 108-068 (200 micrograms kg-1) and -25% and -45% for SBP and DBP respectively with PN 200-110 (200 micrograms kg-1). 3. The duration of the reduction in BP increased with the dose and was much longer for PN 200-110 (180 min for SBP) than for PY 108-068 (20 min for SBP). 4. A tachycardia was associated with the decrease in BP which did not differ at 200 micrograms kg-1 between PY 108-068 (+ 108 beats min-1) and PN 200-110 (+ 103 beats min-1). Baroreflex sensitivity was not significantly increased by either drug. 5. The 5 repeated injections of PY 108-068 and PN 200-110 evoked similar responses. 6. In conclusion, both compounds exhibited marked hypotensive properties. PN 200-110 appeared to be more suitable for further development since its effects were found to be greater and much longer lasting than those of PY 108-068.

Animals↗
PubMed1988

NE turnover in genetically hypertensive rats of Lyon strain. I. Brain nuclei.

Several indirect evidences of alterations in the central catecholaminergic structures were obtained in genetically hypertensive rats. Because they could be of pathogenetic value, we measured, in the present work, the in vivo turnover (TO) of norepinephrine (NE) in brain areas of 5- and 22-wk-old genetically hypertensive (LH) rats of the Lyon strain, and their simultaneously selected normotensive (LN) and low blood pressure (LL) controls. Among the changes observed, the increased TO of NE in the A2 and A6 regions of 5-wk-old LH rats and its decrease in the posteroventral hypothalamic nucleus of 22-wk-old LH animals appeared likely to compensate for hypertension. On the contrary, the decreased TO of NE in the anterior hypothalamic nucleus observed at 5 wk and in the A6 and A1 areas at 22 wk of age in LH rats could participate in the development or the maintenance of hypertension. Above all, it was postulated that the increased TO of NE found in the A7 region of 5-wk-old LH rats could play a primary role in the pathogenesis of hypertension in the Lyon model.

Aging↗
PubMed1988

NE turnover in genetically hypertensive rats of Lyon strain. II. Peripheral organs.

The peripheral sympathetic nervous system (SNS) is a major determinant of blood pressure and is likely to be involved in the pathophysiology of hypertension. Because SNS activity varies among organs, we measured the in vivo turnover (TO) of norepinephrine (NE) in seven organs of 5- and 22-wk-old genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains. The TO of NE was found normal in the superior cervical ganglia and decreased in the heart of 5-wk-old LH rats compared with both LL and LN controls. This suggests that sympathetic cardiac innervation may not be involved in the development of hypertension. On the contrary, an increased TO of NE in the kidney cortex and an elevated TO of dopamine associated with an increased epinephrine content in the adrenal medulla were observed in 5-wk-old LH rats, which could participate in the development of hypertension in the Lyon model.

Adrenal Medulla↗
PubMed1988

Brain and peripheral noradrenergic neuron activity in developing genetically hypertensive rats of the Lyon strain.

In order to estimate the alterations in the activity of noradrenergic brain areas and peripheral nerves in relation to genetic hypertension, the concentration and the in-vivo turnover (TO) of norepinephrine (NE) were measured in various brain and peripheral structures of 5 and 22 week-old genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) male rats of the Lyon strains. LH rats significantly differed from both LN and LL age-matched controls by: i) at 5 weeks, a lowered TO of NE in the anterior hypothalamic region and the median eminence; an elevated TO of NE in the A6 and A7 areas, and in the kidney cortex, and an elevated TO of dopamine in the adrenal medulla, ii) at 22 weeks, a decreased TO of NE in A1 and A6 regions and an increased TO of NE in the thoracic spinal cord. These data suggest that an increased activity of the renal nerves and of the adrenal medulla, possibly originating in central alterations of noradrenergic neurons, could be involved in the development of hypertension in the Lyon strain.

Animals↗
PubMed1988

[Influence of hypertension and age on the sympathetic and parasympathetic components of cardiac baroreflex in the conscious rat].

The influence of blood pressure (BP) level and age on the baroreflex sensitivity (BRS) and its autonomic nervous components was studied in genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strains at 5, 9, 13 and 70 weeks of age. BRS was computed as the slope of the closest relationship, according to the cardiac response delay, between systolic blood pressure (SBP) and heart period changes induced by phenylephrine injections (3 micrograms/kg, i.v.) BRS and the relative importance of vagal and sympathetic components were determined in 4 conditions: 1) basal; 2) after beta-adrenergic blockade (propranolol, 2 mg/kg i.v.); 3) after vagal blockade (atropine, 2 mg/kg i.v.); 4) after vagal and beta-adrenergic blockade (atropine and propranolol, 2 mg/kg, i.v. each). At 5 weeks of age, BRS did not differ between the 3 strains (0.50 +/- 0.05, 0.69 +/- 0.10 and 0.62 +/- 0.09 ms/mmHg in LH, LN and LL rats respectively). In LN rats, BRS increased sharply between 5 and 9 weeks (1.25 +/- 0.12 ms/mmHg) and then remained stable until 70 weeks of age (1.19 +/- 0.14 ms/mmHg). Such an increase did not occur in LH rats and their BRS value was lower than that of LN and LL controls starting from 9 weeks of age. The vagal component of BRS was found to be more important than the sympathetic one in adult rats whatever the strain (80 p. 100 vs 20 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗