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Biomedical subjects

M Carmignani

Publications and source records attributed to M Carmignani.

At least 37 records · Page 2Linked to original sources

Zinc and copper in tissues of rats with blood hypertension induced by long-term lead exposure.

Male Sprague-Dawley rats received for 14 months 0, 15, 30 and 60 micrograms/ml of lead in drinking water. Both blood pressure and tissue lead were augmented with a dose-response effect, while cardiac inotropism was increased only in the rats treated with 60 ppm of lead. In the exposed animals, zinc and copper were unchanged in kidneys and testicles and augmented in the brain, while copper, but not zinc, was reduced in the heart. These data suggest a possible relation between the modifications of copper and zinc metabolism and the effects of lead on cardiovascular homeostasis.

Administration, Oral↗

Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats.

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.

Animals↗

Kallikrein-kinin,enkephalin, renin-aldosterone and catecholamine systems in the vanadate (as vanadyl)-induced arterial hypertension.

Exposure to vanadate was found to induce arterial hypertension through effects on renin-angiotensin-aldosterone, renal peptidergic, and central and peripheral catecholaminergic systems. Vanadate increased, mainly in vascular myocells, both receptor-operated Ca2+ channel- and cyclic-AMP-dependent availability of Ca2+ for contractile processes. Vanadate was selectively accumulated by tissues in the +4 oxidation state (vanadyl).

Aldosterone↗

Physiologic role of the peripheral enkephalinergic system in regulating cardiovascular homeostasis: evidence of interactions with the renin-angiotensin and kallikrein-kinin systems.

On isolated heart preparation, it was found that Leu5-Enkephalin (Leu5-ENK) did not influence the cardiac function. On the other hand, Leu5-ENK induced a specific dose-related inhibition, in the cardiac perfusate, of the activities of kininase II (KII) and angiotensin converting enzyme (ACE) (but not of kininase I-KI). Instead no detectable alterations of the above enzymatic activities with the used concentrations of Leu5-ENK were observed in vitro. This opioid also increased specifically the effects induced by some of the autacoids, related to both renin-angiotensin and kallikrein-kinin systems, on the KII and ACE activities. A specific correlation between these Leu5-ENK-induced modifications and the functional responses of the heart to the same autacoids was observed. Naloxone (NAL) and more significantly ICI 174864 (ICI) opposed or reversed the inhibitory effect of the used opioid whereas they had neither inhibitory nor synergic effect on both KII and ACE activity by themselves. The possible physiologic role of the enkephalins in regulating cardiovascular function by acting peripherally on some humoral systems through modulatory mechanism was discussed.

Animals↗

A human monoclonal autoantibody isolated from a patient with infectious mononucleosis reactive with both self antigens and Epstein-Barr virus nuclear antigen (EBNA).

In order to investigate the mechanism(s) by which Epstein-Barr virus (EBV) induces the outcome of autoantibodies during infectious mononucleosis (IM), a human IgM (k) monoclonal antibody to cytoskeletal filaments of epithelial cells has been prepared by EBV transformation of peripheral blood B lymphocytes obtained from a patient with IM. The antibody was also found to react with smooth muscle of frozen sections of human stomach tissue by immunofluorescence, and with the Epstein-Barr nuclear antigen (EBNA) by an enzyme-linked immunosorbent assay. These findings demonstrate at the clonal level the epitope homology between host's cell antigens and EBV-encoded nuclear antigen, which might have relevance in EBV-induced autoimmunity.

Antibodies, Monoclonal↗

Ultrastructure of the testis in rats with blood hypertension induced by long-term lead exposure.

Male Sprague-Dawley rats received 60 micrograms/ml of lead (as acetate) in drinking water for 18 months. Their blood pressure and cardiac inotropism were increased. Lead was augmented in blood, kidney and brain, but not in testis. Examination by light microscopy of the organs did not reveal alterations. Ultrastructural examination of the testis with both transmission and scanning electron microscopy (EM) did not evidence modifications in the external part of the seminiferous tubules, in the spermatogenetic cells and in the connective tissue including the Leydig cells; only Sertoli cells presented increased size of lysosomes.

Animals↗

Neurohumoral blood pressure regulation in lead exposure.

Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 micrograms/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity by acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of alpha 2-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular beta-adrenergic and dopaminergic receptors. The cAMP-dependent availability of Ca2+ for contractile mechanisms of the cardiovascular muscle cells was affected by lead.

Animals↗

Mechanisms of cardiovascular regulation in male rabbits chronically exposed to cadmium.

Male rabbits received 20 micrograms/ml of cadmium in drinking water for nine months. At the end of the treatment aortic vascular resistance was increased, whereas maximum rate of increase in left ventricular pressure, aortic blood flow, stroke volume, cardiac output, left ventricular minute work, and left ventricular stroke work were reduced. Arterial blood pressure, heart rate, and the index of myocardial oxygen consumption were not modified. The exposed rabbits also showed reduced pressor responses to vagotomy, increased cardiovascular responses to angiotensin I and II and isoprenaline, and lower responses to serotonin and guanethidine; the bradycardia induced by clonidine was augmented; the cardiovascular effects of bilateral carotid occlusion, hexamethonium, phenylephrine, histamine, acetylcholine, tyramine, papaverine and verapamil were unaltered. In the treated rabbits cadmium was appreciably higher in the kidney than in the heart; however, renal concentrations of cadmium were lower than those reported as critical for workers exposed to cadmium. Zinc was increased in the kidney but not in the heart, whereas copper remained unchanged in the examined organs. In rabbits treated with cadmium the increased aortic vascular resistance and the reduced myocardial contractility contribute to preserve a haemodynamic equilibrium without alteration of blood pressure and heart rate; the question of whether a similar condition may be present in people exposed to cadmium with normal cardiovascular parameters is discussed.

Animals↗

Metabolic fate and cardiovascular effects of arsenic in rats and rabbits chronically exposed to trivalent and pentavalent arsenic.

Male rats and female rabbits exposed for eighteen and ten months, respectively, to 50 micrograms/ml of trivalent arsenic (As III) in drinking water showed reduction of stroke volume (SV) and cardiac output (CO) and increase of vascular resistance (VR), while no cardiovascular change was observed in male rats receiving 50 micrograms/ml of pentavalent arsenic (As V) for eighteen months. The exposed animals showed specific alterations in some neurohumoral and effector mechanisms regulating cardiovascular function (CF). Elevated levels of urinary As were found in all treated groups. However, there were significant differences in the urinary levels of dimethylarsenic acid (DMA), monomethylarsenic acid (MMA) and inorganic As, which depended on both animal species and the valency state of As. Thus, As(III) was methylated to a greater extent than As(V) in rats, with less elimination of inorganic As, while rabbits had a lower capacity to methylate As and to retain As in tissues than rats. Either cardiovascular effects or metabolism of As seemed to depend on its valency state and animal species.

Animals↗

Long-term exposure to cadmium and cardiovascular alterations in the rabbit.

Some mechanisms regulating cardiovascular function (CF) were investigated in male rabbits exposed for ten months to 20 micrograms/ml of cadmium (Cd) in drinking water. Cd reduced cardiac inotropism (CI), increased aortic vascular resistance (AVR) and altered cardiovascular reactivity by acting on renin-angiotensin, serotonin, sympathetic and vagal parasympathetic systems. Cd levels were higher in the aorta than in the heart. Renal Cd content was lower than that reported as critical for Cd-exposed workers. Zinc (Zn) was increased only in the kidney and copper (Cu) was unchanged in the organs studied. It was shown that humoral, neurogenic and metabolic mechanisms are involved in the Cd-induced alterations of CF.

Animals↗

Cardiovascular responsiveness to physiological agonists of male rats made hypertensive by long-term exposure to cadmium.

The mechanisms by which cadmium may affect cardiovascular regulation are controversial. In this study, we investigated haemodynamics and cardiovascular reactivity to various physiological agonists in anaesthetized male Sprague-Dawley rats which received, for 190 days, deionized drinking water containing 0 (control), 10 and 20 micrograms/ml of cadmium (as acetate). Systolic and diastolic blood pressure, as well as cardiac inotropism, were increased in a similar manner in the two groups of treated rats. Heart rate was reduced in the rats exposed to the higher dose of cadmium, while no electrocardiographic alteration was demonstrated. Cadmium exposure reduced the pressor responses following intravenous norepinephrine (0.25-1 microgram/kg), angiotensin I (0.25-1 microgram/kg) and higher doses of epinephrine (0.50 and 1 microgram/kg) as well as the depressor responses to bradykinin (0.40-1.6 microgram/kg). On the other hand, the exposed rats showed an increased vascular responsiveness to the beta-adrenoceptor stimulating effects of lower doses of epinephrine (0.125 and 0.25 microgram/kg). Moreover, the effects on blood pressure, heart rate and cardiac inotropism of graduated doses of intravenous acetylcholine, angiotensin II, histamine and serotonin were unchanged. Cadmium was accumulated in the kidney of the treated rats at levels similar to those found in exposed humans. Renal copper and zinc were also augmented, possibly in relation to the cadmium-induced synthesis of metallothionein, a protein able to bind different metals. On the whole, this study suggests that cadmium affects several neurohumoral mechanisms that regulate cardiovascular function. It is likely that the changes in these mechanisms have additive effects, under a possible influence of genetic and/or environmental variables, in determining cardiovascular alterations.

Acetylcholine↗

Cardiovascular homeostasis in rats chronically exposed to mercuric chloride.

Two groups of male Sprague-Dawley rats received from weaning 50 micrograms/ml of mercury as mercuric chloride (HgCl2) in drinking water for 320 and 350 days. Hg exposure increased cardiac inotropism, without chronotropic changes, in both groups, and induced arterial hypertension in the rats exposed for 350 days. In the exposed rats, cardiovascular responses to the stimulation of peripheral alpha and beta adrenoceptors were decreased and increased, respectively, possibly through a reduced intracellular availability of calcium ions for contractile mechanisms. Hg exposure did not affect either vagal or sympathetic activity or cardiovascular reactivity to several physiological agonists. On the other hand, Hg exposure induced baroreflex hyposensitivity and produced a drastic alteration of the levels of copper and zinc in brain and kidney.

Animals↗

Adverse interaction between acetazolamide and anticholinesterase drugs at the normal and myasthenic neuromuscular junction level.

At skeletal neuromuscular junction level in vivo and in vitro experiments have revealed an adverse reversible interaction between acetazolamide and anticholinesterase drugs. Acetazolamide (500 mg, i.v.) prevented the increase in amplitude induced by edrophonium (5 mg, i.v.) on the action potentials derived by surface electrodes from the opponens pollicis muscle of patients affected by myasthenia gravis, when the median nerve was stimulated at the wrist by low frequency repetitive pulses (5/s). Similarly, acetazolamide significantly reduced the contractile force potentiation induced by neostigmine on the rat phrenic-diaphragm preparation, indirectly stimulated by means of low frequency repetitive pulses on the motor nerve. Under such experimental conditions acetazolamide did not show any significant action of its own, but it counteracted the effects of anticholinesterase drugs only when tested before them. It is hypothesized that the effect of acetazolamide on the skeletal neuromuscular junction may occur at presynaptic and/or postsynaptic sites by a mechanism only partly ascribable to the well-known carbonic anhydrase inhibitory activity of this drug.

Acetazolamide↗

Mechanisms in cardiovascular regulation following chronic exposure of male rats to inorganic mercury.

In this study we verified the possibility that chronic exposure to inorganic mercury may induce hemodynamic changes in the rat by affecting some neurogenic and/or humoral mechanisms regulating cardiovascular function. For this reason, aortic blood pressure, maximum rate of rise of the left ventricular pressure, heart rate, and electrocardiogram were monitored under pentothal anesthesia in rats which received 50 micrograms/ml of mercury (as HgCL2) in drinking water for 320 days and in control rats. No pressor or electrocardiographic changes were found in mercury-treated animals, which showed increase of cardiac inotropism and decrease of the pressor and inotropic responses to bilateral carotid occlusion. Cardiovascular responses to bilateral vagotomy and iv hexamethonium under vagotomy were unchanged in the mercury-exposed rats. In these animals both pressor and inotropic responses to iv norepinephrine and to higher doses of epinephrine were reduced, while the vascular beta-adrenergic response to 0.125 micrograms/kg of iv epinephrine was potentiated. Cardiovascular responses to acetylcholine, angiotensin I, angiotensin II, bradykinin, histamine, and serotonin did not differ in the two groups of rats. These results indicated that chronic mercury exposure affects cardiovascular function by interfering with the baroreflex mechanisms and/or the reactivity to catecholamines. Higher amounts of mercury were found in kidney, but the metal was significantly accumulated also in urine, blood, and brain. Mercury exposure greatly increased the levels of copper and zinc, but not that of iron, in brain and kidney. The increased accumulation of copper and zinc in tissues may be related in part to the mercury-induced synthesis of metallothionein, a protein able to bind these essential metals. It may be suggested that zinc and copper interact with mercury in inducing cardiovascular changes.

Animals↗