Biomedical subjects

M C Breschi

Publications and source records attributed to M C Breschi.

At least 37 records · Page 2Linked to original sources

PubMed1995

Age-related changes in the noradrenergic pattern and receptor responses of the rat cardiovascular system after repeated microwave exposure.

In the present research the effect of repeated microwave exposure on the noradrenergic pattern by histofluorescence method and on receptor-mediated responses using alpha and beta agonists in myocardium and aorta of young-adult and aged rats was studied. Young-adult irradiated rats showed an increase in noradrenergic innervation more marked in myocardial tissue, while an increase in maximal response to the agonist was found only at aortic level. Aged stressed rats exhibited an increase in fluorescent fibres at atrial and aortic level, but in the atrial section this increase was found to be less evident than in young-adult animals. Functional data in aged rats revealed a more marked decrease in maximal response ratio (M.R.R.) of myocardial tissue than in young-adult rats, together with a noticeable decrease in maximal response at aortic level. These results indicate no direct correlation between morphological and functional data. Participation of both central and peripheral mechanisms is suggested.

Aging↗

PubMed1995

Effects of idrapril calcium on tissue angiotensin-converting enzyme in rats.

Tissue angiotensin-converting enzyme (ACE) inhibition was measured in rats after single intravenous (i.v.) and oral (p.o.) doses of idrapril calcium, and the correlation between peak inhibition and tissue concentration of the drug was investigated. Five minutes after idrapril calcium (3 mg/kg i.v. as free acid), ACE in the examined tissues (serum, lungs, kidneys, heart, aorta, adrenals, testes, and brain) showed > 50% inhibition, always associated with measurable amounts of idrapril. After 90 min, ACE activity was still inhibited only in serum, lungs, kidneys, and aorta, recovering to basal values by 8 h in all samples but serum. Oral idrapril calcium (30 mg/kg) produced > 50% peak ACE inhibition in serum, lungs, and kidneys, in which measurable levels of the drug were detected, and in the aorta, where idrapril was not detected. Other tissues showed neither marked inhibition nor measurable drug levels. Kinetics of ACE inhibition in affected tissue mirrored those observed after intravenous administration. Idrapril, despite its hydrophilic nature, is able to reach extravascular tissues and to inhibit local ACE. However, in no tissue did the effect on ACE last longer than in serum and the hypothesis of a peculiar role of tissue RAS in determining the hypotensive activity of idrapril calcium is not supported in rats.

Administration, Oral↗

PubMed1994

The [(methyloxy)imino]methyl moiety as a bioisoster of aryl. A novel class of completely aliphatic beta-adrenergic receptor antagonists.

Previous studies in the field of beta-adrenergic drugs had supported the hypothesis of the existence of a bioisosterism between the [(methyleneamino)oxy]methyl moiety (C = NOCH2, MAOMM) of type B beta-blocking drugs and the aryl (Ar) of type A beta-blocking agents. In the MAOMM, however, the carbon of the CH2 linked to the oximic oxygen possesses a hybridization (sp3) and a geometry different from those of the corresponding carbon of Ar which possesses an sp2 hybridization. Furthermore, in the MAOMM, in its preferred conformation, the unsaturated portion (C = N) is situated in a spatial area which does not correspond exactly to the area occupied by Ar. The formal inversion of the atomic sequence C = NOCH2 of the MAOMM leads to a different type of group, the [(methyloxy)imino]methyl moiety (CH2ON = C, MOIMM), which, in the E configuration, appears to present greater steric and electronic analogies with an Ar, with respect to the MAOMM. On the basis of these observations, some completely aliphatic (E)-N-(3-amino-2- hydroxypropylidene)(alkyloxy)amino derivatives of type C (11a,b and 12a, b) were synthesized, the their beta-adrenergic properties were compared with those of the corresponding [(methyleneamino)oxy]-methyl isomers of type B (19a, b and 20a, b). The similar beta-adrenergic properties of 11, 12 and 19, 20 evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations, are discussed on the basis of considerations regarding the spatial correspondences and electronic analogies between the MOIMM and the MAOMM.

Adrenergic beta-1 Receptor Antagonists↗

PubMed1994

Adenosine enhances the bronchocontractile response to histamine in anaesthetized and curarized guinea pigs through a mechanism partly blocked by hexamethonium.

The ability of adenosine to potentiate the airway narrowing induced by histamine in anaesthetized and curarized guinea pigs has been investigated in order to establish whether it could be ascribed to a modulatory activity by the nucleoside at the neuronal level. Bilateral vagotomy, atropine (2 mg/kg i.v.), and pretreatment with capsaicin (52 mg/kg s.c. 6 days before the experiment) did not result in any significant protection against the enhancement provoked by the nucleoside of the bronchocontractile effect of histamine. On the contrary, the latter was significantly reduced by the ganglionic blocking agent, hexamethonium (10 mg/kg i.v.). Moreover, the effect of adenosine on airway responsiveness to histamine was not modified in animals treated with propranolol (1 mg/kg i.v.) or guanethidine (20 mg/kg s.c. over a period of 2 days). In conclusion, current data suggest that the purine is able, in our experimental model, to potentiate the bronchospasm induced by histamine by means of a mechanism mediated, at least partly, by non-adrenergic-non-cholinergic nerves not related to capsaicin-sensitive afferent neurons.

Adenosine↗

PubMed1994

Noradrenergic innervation and receptor responses of cardiovascular tissues from young and aged rats after acute microwave exposure.

Young and senescent rats were exposed to 2,450 GHz microwaves for 45' and the effects of this treatment on the noradrenergic pattern and beta-cardiac and alpha-aortic receptorial functions were evaluated. In young animals, an increase in noradrenergic innervation was observed, while no functional modification was shown. In aged rats the increase in fluorescent fibers was almost the same as that observed in young rats, but significant variations in functional responses were found. Both at atrial and ventricular levels responses to the beta-agonist isoprenaline were unmodified in their affinity indices, but showed a marked decrease in the maximal responses; by contrast the activity of noradrenaline on the aortic alpha-adrenoceptors showed a great increase in maximal response without changes in the pD2 values. These results suggest that the predominant effect of microwave exposure consists in an increase in the noradrenergic pattern, and this effect is not related to the functional modifications.

Aging↗

PubMed1994

Morphofunctional changes in the noradrenergic innervation of the rat cardiovascular system after varying duration of noise stress.

One, six and twelve hs of exposure to acoustic stress showed different influences on the noradrenergic pattern and receptor function of the rat atria and aorta. Moreover, the lipid content of the adrenal cortex and hepatic glycogen were histochemically evaluated in the same animals to correlate these observations with the previous results. The increase in exposure time induced a corresponding increase in sympathetic innervation, which was more evident at cardiac level. The functional results showed that the potency of the agonists on the alpha- and beta-adrenoceptors does not vary, with the exception of 6-h treatment, which affected beta-receptors. By contrast, the M.R.R. of beta-receptors proved to be modified in all treatments, suggesting that noise stress affected mainly postreceptorial mechanisms linked to beta-adrenoceptors rather than their density or affinity; no significant functional modifications were observed when alpha-receptors were considered.

Adrenal Cortex↗

PubMed1993

Conformationally restrained analogs of sympathomimetic catecholamines. Synthesis, conformational analysis, and adrenergic activity of isochroman derivatives.

In previous papers dealing with the study of the conformations and the biopharmacological activity of conformationally restrained analogs of sympathomimetic catecholamines (NE and ISO), proposals were advanced for the three-dimensional molecular models A, B, and C; these models provided information about the steric requirements for the direct activation of alpha 1, alpha 2,beta 1, and beta 2 adrenoceptors, respectively. The 1-(aminomethyl)-6,7-dihydroxyisochromans 11 and 12 and the 1-(aminomethyl)-5,6-dihydroxyisochromans 13 and 14 (1-AMDICs) are two different types of semirigid analogs of NE and ISO. The alpha 1, alpha 2, beta 1, and beta 2 adrenergic properties of the 1-AMDICs 11-14 were evaluated in vitro, both by radioligand binding assays and by functional tests on isolated preparations, and were compared with those of their parent compounds (NE and ISO). The results of a conformational study carried out by means of both 1H NMR spectrometry and theoretical calculations indicated that, in these 1-AMDICs, the presumed active groups (aryl moiety, amine nitrogen and benzylic ethereal oxygen) are in a spatial relationship corresponding to the one found for NE and ISO in their preferred conformations, which also proved to be the pharmacophoric conformation in the models A-C. By means of a comparison of the stereostructures of the 1-AMDICs 11-14 with their biopharmacological properties, it was possible to obtain a further definition of the model B with respect to the activation of the alpha 2 adrenoceptors; the superimposition of the 1-AMDICs 11 and 12 with the molecular model C made it possible to detect an area of the beta-adrenergic receptors which might hinder the fit of adrenergic drugs that are analogs of catecholamines with these receptors.

Animals↗

PubMed1993

Relation of birthweight to maternal plasma glucose and insulin concentrations during normal pregnancy.

Maternal diabetes mellitus is complicated by fetal macrosomia and predisposes the offspring to diabetes, but recent evidence indicates that a low, not high, birthweight is associated with a higher incidence of Type 2 (non-insulin dependent) diabetes in adult life. To clarify the relationships between maternal glucose and insulin levels and birthweight, we measured oral glucose tolerance and neonatal weight in a large group (n = 529) of women during the 26th week of pregnancy. Women with gestational diabetes (n = 17) had more familial diabetes, higher pre-pregnancy body weight, and tended to have large-for-gestational-age babies. In contrast, women with essential hypertension (n = 10) gave birth to significantly (p < 0.01) smaller babies. In the normal group (without gestational diabetes or hypertension, n = 503), maternal body weight before pregnancy and at term, maternal height, week of delivery, gender of the newborn, and parity were all significant, independent predictors of birthweight, together explaining 23% of the variability of neonatal weight. In addition, both fasting (p < 0.006) and 2-h post-glucose (p = 0.03) maternal plasma glucose concentrations were positively associated with birthweight independent of the other physiological determinants, accounting, however, for only 10% of the explained variability. In a subgroup of 134 normal mothers with pre-pregnancy body mass index of less than 25 kg.m-2, in whom plasma insulin measurements were available, the insulin area-under-curve was inversely related to birthweight (p < 0.02) after simultaneously adjusting for physiological factors and glucose area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Crude extracts and two linear diterpenes from Cystoseira balearica and their activity.

Crude extracts of Cystoseira balearica were submitted to pharmacological investigations. The chloroform-methanol residue caused relaxation of the rat aortic musculature and an inhibitory action on the guinea pig atria. The fractionation of this crude extract gave two active diterpenoids, eleganolone (1) and elegandiol (2), the latter has not previously been isolated from this alga. These pure components, never before tested, showed a higher activity when compared with the crude residue.

Animals↗

PubMed1992

Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors.

The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4-dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7-dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor.

Animals↗

PubMed1992

Effects of subacute exposure to noise on the noradrenergic innervation of the cardiovascular system in young and aged rats: a morphofunctional study.

The effects of subacute noise stress on the noradrenergic pattern and receptor-mediated responses were examined in aorta and atria of young and aged rats. Noise exposure increased the density of noradrenergic fibres and responses to the beta-adrenergic agonist isoprenaline in the cardiac tissue of young animals. In aged rats, the stressing stimulus markedly increased the maximal response to the alpha-agonist on the aortic musculature; on the contrary, a reduced responsiveness to the beta-agonist was observed at the cardiac level, without any noteworthy changes in the noradrenergic pattern in comparison to aged controls. The present results indicate that subacute noise stress induces both morphological and functional modifications of the noradrenergic nervous system and also that after subacute noise stress, morphological changes do not necessarily correspond exactly to functional data; the latter show responses that are more widely differentiated than the morphological ones.

Aging↗

PubMed1992

Vasoconstrictor activity of 8-O-acetylharpagide from Ajuga reptans.

The traditional therapeutic indications for the use of Ajuga reptans (Labiatae) have been investigated. The H2O-soluble part of a crude and partially purified MeOH extract and two isolated iridoids (8-O-acetylharpagide and harpagide), were tested for a biological activity on isolated smooth muscle preparations from guinea pig.

Animals↗

PubMed1992

Changes in airway reactivity to exogenous and endogenous acetylcholine and substance P after anaphylactic bronchoconstriction in anaesthetized guinea-pigs.

1. In anaesthetized, actively sensitized guinea-pigs, the anaphylactic shock induced by antigen aerosol challenge (5 s; 50 mg ml-1) was followed by increase in airway reactivity to both acetylcholine and substance P. In particular dose-response curves to acetylcholine (3-1000 micrograms kg-1 i.v.) and to substance P (5-80 micrograms kg-1 i.v.) obtained in antigen exposed animals were significantly shifted to the left of those performed in control guinea-pigs (exposed to saline aerosol). 2. The hyperreactive phenomenon after antigen aerosol was also evident when capsaicin-induced bronchoconstriction (1-4 micrograms kg-1 i.v.) was tested; the degree of hyperresponsiveness was similar to that observed with acetylcholine and substance P as agonists. 3. The frequency-response curves to vagal stimulation, either cholinergic or NANC in nature, were not significantly modified in guinea-pigs challenged with the antigen in respect to those aerosolized with saline. 4. The data obtained in the present study indicate that the airway hyperresponsiveness present in the animal model used is non-specific, involving both cholinergic and peptidergic effects. On the other hand, the lack of potentiation of the bronchoconstriction response to electrical stimulation might suggest that the establishment of a clear hyperreactive phenomenon is under the control of different mechanisms unrelated to increased bronchial reactivity.

Acetylcholine↗

PubMed1991

Comparative study of postsynaptic alpha-adrenoceptors in aorta obtained from human and other mammalian species.

The alpha-adrenoceptor populations in aortic strips from humans, rats, guinea-pigs and rabbits were investigated in vitro, using specific agonists and antagonists. In rabbit and human preparations the activities of the two agonists tested, noradrenaline and methoxamine, were competitively antagonized by prazosin, whereas in the other animal species prazosin showed a competitive antagonism for methoxamine induced contraction, but an uncompetitive behaviour against noradrenaline. The alpha 2-selective agonists B-HT 920 and detomidine did not elicit any effect on aortic strips up to 10(-3) M. On the basis of these results, alpha 1-receptors seem to represent an homogeneous population in human and rabbit aortae, but not in rat and guinea-pig tissues. On the other hand, the contractile response of noradrenaline and methoxamine on aortic strips from the four animal species examined cannot be ascribed to the activation of postsynaptic alpha 2-receptors. Moreover we present preliminary evidence that rat and guinea-pig aortae do not contain a clear subdivision in alpha 1a- and alpha 1b-receptors.

Adrenergic alpha-Agonists↗

PubMed1991

Differences in activity between noradrenaline and other alpha-agonists in rat vas deferens.

1 The stimulating activity of methoxamine on rat vas deferens differed from that of noradrenaline since it induced a strong rhythmic activity which was not removed by the wash-out of the drug. 2 Clonidine showed a dose-response curve with a pD2 of 5.05 +/- 0.14 and an intrinsic activity value of 0.6 +/- 0.1%; B-HT 920, a specific alpha 2-agonist, elicited a very low stimulating effect (pD2 = 2.87 +/- 0.04; i.a. = 0.08 +/- 0.001). 3 In a calcium-free medium the maximum responses to synthetic alpha-adrenoceptor agonists were reduced by 98 +/- 0.8% compared with the control value. The residual response to noradrenaline, however, was significantly higher (15 +/- 0.9% of the control value). 4 At high concentration of the Ca-channel antagonists, nicardipine and verapamil, only noradrenaline showed a residual response that was resistant to the calcium channel blockers. This residual response was completely inhibited by chloroethylclonidine (10(-5) M). 5 It is proposed that the stimulating activity of the physiological adrenergic agonist, noradrenaline, is more complex when compared to that of synthetic agonists and it might result from an interaction with different alpha-adrenoceptors. 6 Both salbutamol and forskolin were able to abolish the rhythmic activity of methoxamine, suggesting a regulatory role of cAMP on membrane stability.

Adrenergic alpha-Agonists↗

PubMed1990

Adrenergic innervation of the ductus deferens in young and aging rats: a morpho-functional investigation.

The pattern of adrenergic innervation and the responsiveness to alpha-agonists of the epididymal and prostatic portions of the ductus deferens from young and aging rats were examined. The histochemical pictures showed that the distribution of the adrenergic fibres varies between the 2 ends of the ductus deferens, with a greater density in the prostatic portion. Tissues from rats aged 20 months showed the same difference in the adrenergic pattern between the 2 portions. Generally, the fluorescent bundles from the tissues of senescent animals seemed to be more numerous and compact. The functional data appear to be in contrast with the morphological observations, because the epididymal tract of young rats showed the highest responsiveness to alpha-agonists. An inverse correlation between the number of adrenergic fibres and receptor responsiveness is hypothesized.

Adrenergic alpha-Agonists↗

PubMed1989

Synthesis and evaluation of the pharmacological activity of rigid analogues of sympathomimetic catecholamines derived from bicyclo[2.2.1]heptane.

endo-3-Amino-exo-2-(3,4-dihydroxyphenyl)-2-hydroxybicyclo[2.2.1]he ptane (4a) and its N-isopropyl derivative (4b) were synthesized and assayed for their adrenergic activity on various isolated preparations. Compounds 4a and 4b, tested up to a dose of 10(-4) M, did not reveal any activity, either stimulant or blocking, on the alpha- and beta-adrenoceptors. Possible rationalizations of the results obtained, however, are suggested.

Animals↗

PubMed1988

Age-related changes in the recovery of noradrenaline content in sympathetic fibres after reserpine treatment.

The aim of the present study was to evaluate noradrenaline recovery times in sympathetic fibres after reserpine administration by using fluorescence histochemical techniques. The spleen, the kidney, and the large intestine were examined 24 h to 15 d after reserpine treatment, in both young and aged male Sprague-Dawley rats, in order to establish not only the possible differences in recovery times of the various organs, but also if senescence can influence these times. The complete restoration of the noradrenaline content took place sooner in younger rats than in aged ones, and, within the same age-group, the recovery was quicker in the spleen and needed longer times in the large intestine, particularly in aged rats.

Aging↗