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M C Auclair

Publications and source records attributed to M C Auclair.

At least 19 recordsLinked to original sources
PubMed1994

Effect of estradiol on endotoxin-induced changes in steroid hormone levels and lethality in male rats.

We examined the effect of exogenous estradiol on the changes in serum steroid hormone levels induced by a nonlethal dose of Escherichia coli endotoxin in male rats and the deaths due to nonlethal and lethal doses of endotoxin. Injection of estradiol 5 min before a nonlethal dose of endotoxin changed the serum sex steroid hormone response of male rats to endotoxin. The serum estrogen concentrations of estradiol + endotoxin-treated rats decreased by 50% (P < 0.001), while those of the endotoxin-treated rats increased (2- to 5-fold). The serum androgen concentrations of estradiol + endotoxin-treated rats did not change significantly, while those of endotoxin-treated rats dropped to 30-40%, P < 0.001. Exogenous estradiol also appeared to influence the percentage of endotoxin-induced deaths in a dose-dependent manner. It reduced the number of deaths induced by nonlethal (2 mg/kg) dose of endotoxin but increased the number of deaths induced by a highly lethal dose (8 mg/kg). These results, together with the known relationships between estrogen and the immune response, suggest that estrogens affect the course of septic shock in a complex fashion and may have either protective or deleterious effect.

Androgens↗
PubMed1992

Effect of the aromatase inhibitor, 4 hydroxyandrostenedione, on the endotoxin-induced changes in steroid hormones in male rats.

The increase in circulating estrogen concentrations that follows injection of Escherichia coli endotoxin (Endo) may be due to increased aromatase activity. We have therefore analysed the effect of the aromatase inhibitor, 4 hydroxyandrostenedione (4OHA) on the steroid hormone response of male rats, particularly the dramatic increase in estrogens and decrease in androgens, induced by Endo. The concentrations of corticosterone (B), progesterone (P4), 17 alpha hydroxyprogesterone (17 alpha OHP4), androstenedione (delta 4), testosterone (T), estrone (E1) and estradiol (E2) were determined 2 hours after injection of increasing doses of 4OHA with and without Endo. The increase in serum estrogen concentrations and drop in serum androgen levels in response to Endo were blocked by a single dose of 4OHA. The effect of 4OHA appeared to be dose dependent. Low doses (30 mg/kg and 50 mg/kg) induced significant changes in the estrogen and androgen responses, but the high dose (100 mg/kg) blocked all changes in sex steroids induced by Endo. 4OHA did not alter the Endo-induced changes in other steroids.

Analysis of Variance↗
PubMed1991

Endotoxin induced changes in serum estrogen in male rats: influence of testicular maturation.

The influence of acute endotoxin (Endo) administration on adrenal and testicular serum hormones, corticosterone (B), progesterone (P4), 17 alpha OH progesterone (17 alpha OH P4), androstenedione (delta 4), testosterone (T), estrone (E1) and estradiol (E2) was studied in male rats aged 8, 12 and 15 weeks. The present study confirms that the concentrations of circulating steroid hormones in male rats vary with age, and indicate that the adrenal glands mature before the testes. The steroid response to Endo is age-dependent. B, P4, 17 alpha OH P4 was increased and T decreased in all animals. But, there was a very significant increase in estrogens (E1 and E2) and a decrease in delta 4 only in male rats aged 12 weeks and over. The lack of an estrogen response to Endo injection in 8 week-old rats may indicate that the reduced sensitivity (refractory period) to Endo (which has been reported to last until 21 days of age) continues longer. The reduced sensitivity to Endo which occurs in young rats could be due in part to the absence of adrenal-testicular cooperation as a result of partial testicular immaturity.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Dependence on extracellular potassium of the positive inotropic response to St 587, a selective alpha-1 adrenoceptor agonist, in Zucker rat heart ventricle.

The effects of St 587, a selective alpha-1 adrenoceptor agonist, were investigated in non obese and obese Zucker rat heart ventricles. In both groups, the numbers and affinity constants for alpha-1 adrenoceptors were found to be similar. At 4 or 10 mM [K]o, St 587 failed to increase the developed tension whereas at 14 mM [K]o, St 587 significantly increased it in both groups of rats. This effect was reversed by prazosin; St 587 also increased action potential duration at 14 mM [K]o. [K]o is thus important for the occurrence of the inotropic effect of St 587 in 12 week-old Zucker rats, either non obese or obese with reduced beta-adrenoceptor responsiveness. This suggests the participation of phosphoinositide metabolism in the mechanism of St 587 inotropic effect in the rat.

Action Potentials↗
PubMed1988

Influence of prostacyclin and two metabolites on the contractility of cultured rat heart cells.

Heart cells were cultured from newborn rats, and the contractile activity (CA) and beating frequency (BF) were recorded using an electrooptical technique. Myocardial cells were found to be highly sensitive to Prostacyclin (PGI2) since a 10(-11) M concentration increased the BF and CA. Increasing the concentration (2.7 x 10(-10) to 2.7 x 10(-8) M) resulted in a dose-dependent decrease in CA and BF. The stable product of the non-enzymatic degradation of PGI2 (6 Keto PGF1 alpha) was found to be completely ineffective, and the stable product of the enzymatic PGI2 metabolism (6 Keto PGE1) exerted only a dose-dependent (10(-6) to 10(-5) M) positive inotropic effect. PGI2 was also effective in the presence of serum instead of culture medium but the decrease in CA was less marked than in culture medium, probably due to protein-binding of the drug. When the CA was decreased by PGI2, perfusion with the intracellular calcium-releasing and phosphodiesterase inhibiting agent, caffeine, reversed the PGI2-induced negative inotropic effect. These results suggest that PGI2 participates in the regulation of the heart cell contractility. Its metabolite 6 Keto PGEI could also influence heart cell contractility but higher concentrations are needed. Moreover myocardial intracellular calcium availability seems to be influenced by PGI2.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

[Reduced sensitivity of the heart ventricle of obese Zucker rats to isoprenaline].

In heart of genetically obese (fa/fa) 12-week-old Zucker rats, ventricle contractility (4 mM KCl medium), amplitude and duration of slow action potentials (14 mM KCl medium) were less increased by isoprenaline than in heart of non obese (Fa/fa) rats. This difference could be related to a lower reactivity of beta-adrenoceptors in obese rat heart.

Action Potentials↗
PubMed1987

Plasma from cirrhotic patients induces inotropic changes on cultured rat heart cells.

Cultured monolayers of newborn rat heart cells were perfused with plasma from patients with alcoholic liver cirrhosis. The results showed that cirrhotic plasma, when compared to control plasma, depressed contractility of beating cardiac cells. The in-vitro deleterious effects of plasma from cirrhotic subjects on cell cultures were neither related to hemodynamic parameters nor to the levels of plasmatic catecholamines. This study suggests the presence in the plasma of patients with alcoholic liver cirrhosis, of humoral factor(s) which cause depressive effects on rat heart cells in culture.

Animals↗
PubMed1987

Antagonism by E. coli endotoxin of some cardiovascular effects induced in the rat by two alpha 2-adrenoceptor agonists.

E. coli endotoxin (0.01, 0.1 and 1 microgram/kg i.v.) 1 h before alpha 2-adrenoceptor agonists B-HT 933 and clonidine (i.v.) antagonized their bradycardiac and hypotensive effects in intact rats. This antagonism seems not to depend on the presence of the adrenal glands since similar results were obtained in adrenalectomized rats. Endotoxin at higher doses (1 and 10 micrograms/kg) suppressed the hypotensive and reduced the bradycardiac effect of clonidine injected i.c.v. (5 micrograms/kg). In contrast, endotoxin (up to 100 micrograms/kg) did neither increase arterial pressure nor heart rate in the pithed rat. This suggests the participation of a central site of action for endotoxin. However, E. coli endotoxin (1, 10 or 100 micrograms/kg) did not decrease the inhibition by clonidine of the tachycardia induced by stimulation of the cardioacceleratory nerve. This excludes peripheral presynaptic alpha 2-adrenoceptor blockade by endotoxin. Only 100 micrograms/kg decreased the pressor response to clonidine in the pithed rat. These results show that E. coli endotoxin is a potent modificator of the cardiovascular regulation in the rat. It antagonized central alpha 2-adrenoceptor mediated cardiovascular effects at doses lower than those acting on postsynaptic peripheral alpha-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1987

Endotoxin-induced changes in sex steroid hormone levels in male rats.

Intravenous administration of Escherichia coli endotoxin (ENDO) was found to induce profound time and dose dependent changes in the serum steroid hormones, oestrone (E1), oestradiol (E2), corticosterone (B), progesterone (P4), 17 alpha-OH progesterone (17 alpha OHP4), and testosterone (T) of intact male rats. These changes were rapid, with a maximal response at 2 h and a return to close to normal values by 4 h. Non-lethal doses (0.01-2 mg/kg) of ENDO induced large increases in oestrogens (3-9-fold), P4 (4-fold) and B (2-3-fold) and decreased serum T (2-fold). The greatest increase in E2 level was seen with an ENDO dose of 2 mg/kg. Serum E1, E2 and T did not change in response to lethal ENDO doses (4-8 mg/kg); B, P4 and 17 alpha OHP4 levels alone were moderately elevated. Systemic mean arterial pressure was unchanged, except at the highest ENDO dose used. Thus, the hormonal responses are unlikely to be the result of hemodynamic changes. Low doses of ENDO did not produce an increase in serum E1 and E2 in adrenalectomized or orchidectomized rats. These results indicate that oestrogens are largely produced in the testis. The aromatization of the testicular and adrenal androgens can be stimulated by glucocorticoid.

Adrenal Glands↗
PubMed1987

Influence of indomethacin on the endotoxin-induced cardiodepressant effect of serum and steroid hormone changes in male rats.

Escherichia coli endotoxin has been shown to induce a cardiodepressant effect (CDE) and changes in steroid hormone concentrations in the serum of male rats, especially increases in estrogens and a decrease in testosterone. Pretreatment of rats with indomethacin (INDO) abolished these responses to endotoxin. Direct addition of INDO to primary cultures of rat heart cells blocked the cardiodepressant response of these cells to endotoxin-treated rat serum. These data, together with previous results, suggest that relationships between estrogens and CDE are possible, while these two parameters have different time courses and dose dependencies; in any case, the prostanoid system is likely involved since INDO is able to suppress both of them.

Animals↗
PubMed1986

Vascular alpha-adrenoceptor blockade by E. coli endotoxin in the rat.

It has been previously shown that Escherichia coli endotoxin (ENDO) reduces the pressor effect of phenylephrine. This work attempted to define precisely the involvement of vascular alpha-adrenoceptors in this action. The dose-response curves of three alpha-agonists noradrenaline, St 587 and B-HT 933 in pithed rats were shifted rightwards by pretreatment (i.v. injection of 10 and 100 micrograms/kg) with ENDO. ENDO 10 and 30 micrograms shifted the dose-response curve of noradrenaline in perfused rat kidney. It can be suggested that ENDO has a potent blocking action on vascular alpha-adrenoceptors without evident discrimination between alpha 1 and alpha 2 subtypes.

Animals↗
PubMed1986

Potentiated cardiodepressant effect of serum by endotoxin in adrenalectomized rats.

We have previously shown that in intact rats (IT) a sublethal and nonhypotensive dose (2 mg/kg IV) of Escherichia coli endotoxin was able to induce the early and sustained release of a lipid-soluble cardiodepressant factor, decreasing contractility of cultured rat heart cells by about 35%. As a humoral mediation may also be envisaged in cardiac dysfunction observed by other investigators in adrenal insufficiency, this study was designed to assess serum cardiodepressant effects of endotoxin in 6-10-day, saline-maintained, adrenalectomized rats (ADX). In ADX 2 mg/kg endotoxin caused severe hypotension and 100% lethality within the first 90 min. To obtain in ADX a depressant effect of serum on cultured heart cells fairly similar to that observed in IT, it was necessary to reduce the endotoxin dose by about 200 times (0.01 mg/kg). The latter proved sublethal and nonhypotensive in ADX and was without depressant effect of serum in IT. Serum from ADX (no endotoxin) induced a slight but significant decrease by about 9% in cultured heart cell contractility when compared to serum from IT or sham-operated controls. These data show that adrenalectomy confers a cardiodepressant effect on rat serum and potentiates the release of endotoxin-induced cardiodepressant substance(s) without relation to systemic hypotension.

Adrenalectomy↗
PubMed1985

[Effect of substances modifying calcium movement on the contractility of cultured cardiac cells].

Cultured cardiac cells from newborn rats were found to be sensitive to the positive or negative inotropic effect of agents capable of interfering with calcium movements. Calcium entry blockers were found specially potent, since diltiazem and nifedipine were still active at concentration of 1 X 10(-9) M. Such a bioassay system seems therefore convenient to compare the relative potency of drugs belonging to this pharmacological class.

Animals↗
PubMed1984

Early released lipid-soluble cardiodepressant factor and elevated oestrogenic substances in human septic shock.

A cardiodepressant factor (CDF) able to decrease contractile activity of cultured rat heart cells was determined to be located in the lipid-soluble fraction of sera from men in septic shock. This heat-stable CDF has a molecular weight under 1000. Repeated fractionations of sera gave evidence of an oestrone-like chromatographic behaviour. Oestrone, oestradiol and cortisol were immunologically quantified in two groups (recovery and death) of men in septic shock. All of them were elevated in sera from patients with shock. Highest levels of oestrone 4330 pmol 1(-1), (SEM +/- 851, n = 15), oestradiol 1030 pmol 1(-1), (SEM +/- 220, n = 15) and cortisol 1096 pmol 1(-1), (SEM +/- 94, n = 15), were found in patients who failed to recover from shock. However, oestrone levels were the most striking, especially in the male. This study gives evidence for a polarity relationship between the CDF and oestrone, but natural oestrone does not appear to be a direct CDF. Moreover, this study shows that radioimmunoassay of oestrone could be an important index evaluating the severeness of septic shock.

Adult↗
PubMed1983

Depressed isoprenaline vascular response in endotoxic rats.

The injection of a sublethal dose of E. coli endotoxin (0127 B8) to intact rats (2 mg/kg i.v) or adrenalectomized rats (0.01 mg/kg i.v.) depressed hypotensive responses to isoprenaline (0.2, 0.4, 0.8 microgram/kg i.v.) for at least 4 h following endotoxin injection. These findings evidence an early (under 1 h after administration) and long-lasting (over 4 h) depression of the vascular response to isoprenaline in endotoxic rats. This depression was not related to catecholamine adrenal discharge or to the hypotensive and lethal effects of endotoxin.

Adrenalectomy↗
PubMed1983

Indomethacin suppresses the early cardiodepressant factor released by endotoxin in the rat: possible involvement of a prostacyclin-related material.

UNLABELLED: The aim of this study was to determine if a prostaglandin-related material--in particular prostacyclinlike substance--could explain our previous findings showing that a sublethal dose of endotoxin caused the early release of a serum lipid-soluble factor able to decrease various activities of cultured rat heart cells (CRHC) through an intracellular calcium dysregulation. Sera were sampled from rats 4 h after administration of 2 mg/kg E coli endotoxin (E) and their cardiodepressant effect on CRHC determined by an electrooptical technique. E-treated rat serum (ETRS) cardiodepressant effect was compared to that of 0.1 ng/ml prostacyclin (PGI2) and of 0.029 ng/ml nifedipine, a calcium antagonist. The reversal effect of caffeine, a substance known for its positive inotropic effect by increasing intracellular calcium availability at the sarcoplasmic reticulum site, has been tested against the depressant effect of ETRS, PGI2, and nifedipine. RESULTS: 1) Compared to control, serum from endotoxin-treated rats with or without imidazole pretreatment depressed contractility of CRHC in a similar fashion, whereas pretreatment with indomethacin had a much less marked effect; 2) PGI2, nifedipine, and ETRS depressed CRHC contractility in much the same way; 3) caffeine reversed the depressant effect of PGI2 and ETRS, but was much less effective against nifedipine effect. These results suggest that the cardiodepressant effect of ETRS is mediated by a prostaglandinlike substance, other than thromboxane, acting through reduced intracellular calcium availability. PGI2 or PGI2-related material is consistent with such a depressant effect and such a mechanism.

Animals↗