PubMed Health⌕ Search

Biomedical subjects

F Ledda

Publications and source records attributed to F Ledda.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effects of opioid drugs on capsaicin-sensitive neurones in guinea-pig atria.

Transmural nerve stimulation of isolated guinea-pig atria in the presence of atropine induced a biphasic positive inotropic effect but only a slow increase in contractility (NANC response) in atria obtained from 6-hydroxy-dopamine-pretreated animals. The latter effect disappeared after exposure of the preparations to capsaicin. The effects of some opioid peptides were investigated on NANC responses. [D-Ala2,D-Leu5]enkephalin (DADLE) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.1-10 microM) inhibited the cardiac response to transmural nerve stimulation in a dose-dependent and naloxone-sensitive manner. Dynorphin-(1-13) and morphine, at 10-fold higher concentrations (1-10 microM), reduced the response in a naloxone-sensitive manner. Naloxone alone however did not affect the response. Opioid peptides were not able to reduce the positive inotropic effect induced by calcitonin gene-related peptide (CGRP), or the increase in cardiac contractility produced by capsaicin. These results suggest that opioid receptors exert a modulatory role on peripheral terminals of capsaicin-sensitive sensory nerves.

Animals↗
PubMed1989

Indirect evidence for a role of prostaglandins as second messengers of the prejunctional effect of opioids in guinea-pig ventricular preparations.

The cardiac response to adrenergic nerve stimulation was dose dependently reduced in a statistically significant manner by 1-10 microM dynorphin-(1-13) in isolated atria, and by 0.1-1 microM dynorphin-(1-13) in guinea-pig ventricular preparations. The inhibitory effect of dynorphin was maintained in atria that had been pretreated with two cyclooxygenase inhibitors at concentrations that induce an 80% inhibition of the enzyme, namely indomethacin 3 microM and acetylsalicylic acid 200 microM. The inhibitory effect of dynorphin disappeared in similarly pretreated ventricular preparations. These results suggest that, whilst the mediation of the effect of dynorphin is carried out mainly by specific opioid receptors in the atrial section, in the ventricular tissue it occurs through the endogenous prostanoid system.

Animals↗
PubMed1989

Interference of WEB 2086 and BN 52021 with Paf-induced effects on guinea-pig trachea.

1. The thienotriazolodiazepine WEB 2086 and the gingkolide BN52021 have been evaluated as antagonists of Paf-acether (Paf) by studying their effects on Paf-induced relaxation and Paf-induced prostaglandin E2 (PGE2) production in histamine-contracted guinea-pig tracheal preparations. 2. Relaxation induced by Paf 4 microM in histamine-contracted guinea-pig tracheal preparations was 39.67 +/- 3.5% (n = 30). At the same concentration, Paf significantly increased PGE2 production from histamine-contracted guinea-pig tracheal preparations. 3. WEB 2086 inhibited in a dose-related manner (IC50 = 21.2 nM) the relaxant effect induced by Paf and, at 1 microM, suppressed Paf-induced release of PGE2. 4. BN 52021 100 microM inhibited to about 60% Paf-induced relaxation of histamine-contracted guinea-pig tracheal preparations, but completely abolished Paf-induced increase in PGE2. 5. Both antagonists had no effects on relaxations induced by arachidonic acid 10 microM or PGE2 0.1-1 microM in histamine-contracted guinea-pig tracheal preparations. 6. The results are consistent with the presence of specific Paf receptors in guinea-pig trachea and indicate that a relaxant prostanoid, namely PGE2, at least partially mediates Paf-induced relaxation in this experimental model.

Animals↗
PubMed1989

Effect of lithium chloride on the neurotransmitter release from adrenergic nerve terminals of guinea-pig atria.

Lithium chloride at 1 and 10 mM produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals, without affecting myocardial contractility in electrically stimulated guinea-pig atria. This effect was calcium-independent and was also present in preparations superfused with 10 mM myoinositol. Moreover, 10 mM lithium chloride reduced the positive inotropic effect of tyramine. These results indicate that lithium reduces the evoked release of noradrenaline from the adrenergic nerve endings, probably lowering the content of releasable neurotransmitter.

Animals↗
PubMed1988

Clinical experiences with Ro 15-1788 (anexate) in benzodiazepine and mixed-drug overdoses.

Benzodiazepine overdose is the most common of admission to the Toxicological Unit of the University of Florence. The aim of this study has been to evaluate the efficiency of Ro 15-1788 in benzodiazepine and mixed drug overdoses. The administration of Ro 15-1788 was followed by a quick reversal of central nervous system depression and was more effective in benzodiazepine overdoses than in mixed drug overdoses. The dose was titrated individually and the range 2-10 mg was effective according to the conditions of the patient. In some cases, the comatose state relapsed; further administration of Ro 15-1788 again promptly reversed the condition. On awakening, two patients displayed anxiety and restlessness.

Adult↗
PubMed1987

On the presence of opioid receptors in guinea-pig ventricular tissue.

The cardiac response to sympathetic nerve stimulation, induced by trains of field pulses, was studied in isolated guinea-pig ventricular strips. Dynorphin-(1-13) and [D-Ala2, D-Leu5]enkephalinamide, but not morphine, reduced, in a dose-dependent manner, the cardiac sympathetic response. The effect of the two opioid peptides was antagonized by naloxone. The opioid agonists did not affect the response to exogenous noradrenaline. Neither naloxone nor a mixture of peptidase inhibitors modified the cardiac response to sympathetic nerve stimulation.

Animals↗
PubMed1986

In vitro evaluation of the beta-blocking and electrophysiological properties of mepindolol.

The electrophysiological and beta-blocking effects of mepindolol have been examined in isolated guinea-pig preparations and sheep cardiac Purkinje fibers. Mepindolol did not show selectivity for blocking the chronotropic and inotropic responses to isoprenaline on isolated guinea-pig preparations, and was practically equally potent in blocking the effect of isoprenaline on isolated guinea-pig trachea. Mepindolol 10(-7) M fully antagonized the positive chronotropic effect of isoprenaline (10(-7) M) in Purkinje fibers. However, normal automaticity, action potential characteristics, effective refractory period, membrane responsiveness of Purkinje fibers were unaffected by mepindolol up to 10(-6) M. On the whole, mepindolol appears to be a potent beta-blocker with no cardioselectivity, exerting membrane depressant effect only at concentrations 100-1000 times higher than those exerting effective beta-blockade.

Adrenergic alpha-Antagonists↗
PubMed1986

Effects of dl-methadone on the response to physiological transmitters and on several functional parameters of the isolated guinea-pig heart.

The effects of high concentrations of dl-methadone (1-10 microM) on several parameters of cardiac function were studied in isolated guinea-pig heart preparations. The opioid agonist dose-dependently potentiated the inotropic cardiac response to sympathetic nerve stimulation; this effect was naloxone-insensitive and was antagonized by an increase in extracellular calcium concentration. Moreover, methadone enhanced the dose-inotropic response curve of exogenous noradrenaline. The cardiac response to parasympathetic stimulation was antagonized by the drug through a postsynaptic effect; the responses to histamine and isoprenaline were also antagonized in a noncompetitive way. The spontaneous rate and contractility of atrial preparations were depressed by methadone concentrations above 1 microM; the functional refractory period was increased and the maximal driving rate was reduced at the same range of concentrations. All the above mentioned effects were naloxone-insensitive. In isolated sheep Purkinje fibers methadone, at concentrations of 10 microM and higher, significantly affected the transmembrane action potential parameters, by chiefly decreasing the maximum rate of depolarization and increasing the action potential duration. It was concluded that high concentrations of dl-methadone are able to affect several parameters of cardiac function through an unspecific mechanism different from the stimulation of opiate receptors.

Action Potentials↗
PubMed1985

Sensitivity to dynorphin-(1-13) of the presynaptic inhibitory opiate receptors of the guinea-pig heart.

Dynorphin-(1-13) at the concentrations of 1-10 microM, produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals in guinea-pig atria pretreated with peptidase inhibitors. This inhibitory effect was competitively antagonized in a dose-dependent manner by 5 and 10 microM naloxone. Since dynorphin-(1-13) did not modify the dose-inotropic effect curve of exogenous noradrenaline, it was concluded that the depressant effect of the opioid agonist was due to the stimulation of the presynaptic inhibitory opiate receptors belonging to the kappa subtype.

Animals↗
PubMed1985

Cardiodepressant effects of ethanol on guinea-pig atria: presynaptic and postsynaptic components.

Ethanol, at concentrations ranging from 0.5 to 1.5%, depressed myocardial contractility of electrically-stimulated guinea-pig atria. This effect was evident in preparations bathed with a low calcium concentration, but was progressively reduced by increasing the extracellular calcium. The same concentrations of ethanol produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals. This effect was again calcium-dependent. These results support the hypothesis that the pre- and postsynaptic components of the cardiodepressant effects of ethanol are due to a reduction in calcium availability both at the nerve endings and in the contractile cells.

Animals↗
PubMed1985

Influences of age on the positive inotropic effect mediated by alpha- and beta-adrenoceptors in rat ventricular strips.

The positive inotropic effect of phenylephrine (in the presence of atenolol) and isoprenaline was studied in isolated right ventricular strips obtained from Wistar rats aged 2 weeks, 3 months, and 26 months. The positive inotropic effects induced by phenylephrine and isoprenaline were higher in the 2-week-old than in the 3- or 26-month-old rats. The typical 'alpha-type' or 'beta-type' responses were induced by phenylephrine (plus atenolol) or isoprenaline, in all the age groups. The EC50 values for the alpha-mediated positive inotropic effect decreased with age, while the EC50 value for the positive inotropic effect of isoprenaline increased in the senescent heart. These results suggest an enhanced alpha-adrenergic sensitivity in the senescent heart.

Aging↗
PubMed1977

Studies on the positive inotropic effect of dopamine in the guinea-pig heart.

The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.

Animals↗
PubMed1977

A histamine-induced decrease of action potential duration in cardiac muscle mediated by the H2 receptors.

The effects of histamine (10(-7)--10(-5) M) on the cardiac action potential have been studied in ventricular strips of guinea pig heart, electrically driven at a constant rate. A decrease of action potential was constantly observed at histamine concentrations above 10(-6) M. No significant variations of the other electrophysiological parameters were induced by the amine. The decrease in the duration of the action potential was blocked by burimamide at a concentration (10(-4) M) which induced only a slight changes in action potential outline. It is suggested that the shortening of the repolarization phase induced by histamine is due to the H2 receptor-mediated activation of the calcium inward current, which can increase the intracellular calcium concentration influencing the potassium permeability.

Action Potentials↗
PubMed1976

Frequency dependence of the alpha-adrenoceptor-mediated positive inotropic effect in guinea pig heart.

Evidence for the role of alpha-adrenoceptors in the production of a positive inotropic effect has been obtained chiefly in heart preparations stimulated at a low rate (1 or 1.4 Hz). However, our previous results suggested that the alpha-receptor-mediated positive inotropic effect could be frequency dependent. In the present study cumulative concentration-inotropic effect curves were obtained in guinea pig ventricle strips treated with adrenaline and stimulated at 1 and at 2.5 Hz. Phentolamine (3 X 10(-6) M) and practolol (10(-6) M) were employed as antagonists. Phentolamine antagonized the effect of low concentrations of adrenaline (10(-9)-10(-8) M) in preparations driven at 1 Hz, but did not modify the curve of the agonist at the higher stimulation rate. In preparations driven at 1 Hz, practolol antagonized the effect of adrenaline at concentration above 3 X 10(-8) M without affecting the curve at lower concentrations, the beta-blocker competitively anatagonized the effect of the agonist at 2.5 Hz. It was concluded that a shortening of the interval between beats abolishes the alpha-mediated positive inotropic effect.

Animals↗