Biomedical subjects

S Maione

Publications and source records attributed to S Maione.

At least 37 records · Page 2Linked to original sources

PubMed1998

L-Cysteinesulfinic acid modulates cardiovascular function in the periaqueductal gray area of rat.

L-Cysteinesulfinic acid (CSA) involvement in modulating periaqueductal gray (PAG) pressor neurons has been evaluated in the rat. Intra-PAG CSA induced an increase in mean blood pressure partially antagonized by (2S)-alpha-ethylglutamic acid (EGA), a group II metabotropic glutamate receptors (mGluRs) antagonist. Conversely, the NMDA antagonist, DL-AP5, or the mGluRs antagonists, (+)-MCPG, UPF523, or (RS)-alpha-methylserine-O-phosphate (MSOP), were devoid of any activity on the CSA effect. These data show that the excitatory amino acid CSA, probably by stimulating an mGluR, contributes with glutamate in modulating cardiovascular function at the PAG matter.

Animals↗

PubMed1997

May age onset be relevant in the occurrence of left ventricular hypertrophy in Friedreich's ataxia?

BACKGROUND: Although heart involvement has been widely reported in Friedreich's ataxia (FA), which is the most prevalent of the spino-cerebellar degenerative diseases, the reason that cardiac abnormalities develop has not been yet established. HYPOTHESIS: The investigation was undertaken to study the prevalence and characteristics of cardiac abnormalities in patients with FA and to evaluate whether the presence of left ventricular hypertrophy could be predicted. METHODS: In all, 75 patients with FA and 16 patients with late onset FA (LOFA) disease were investigated for cardiac abnormalities using noninvasive methods. RESULTS: A significant (p < 0.01) difference in the age onset (9.8 +/- 3.9 years) was found in 31 of the 75 patients with FA (41%) who showed left ventricular hypertrophy (LVH) at echocardiographic examination compared with the remaining 44 patients with FA without LVH (12.6 +/- 4.3 years). Moreover, none of the 16 patients with LOFA (age onset 26.5 +/- 4.2 years) showed abnormalities at echocardiographic examination. A significant (p < 0.01) concordance in the familial distribution of hypertrophy was also found. CONCLUSION: These data suggest that the earlier the disease develops the more frequently LVH occurs.

Adolescent↗

PubMed1997

Effects of imipramine on raphe nuclei and prefrontal cortex extracellular serotonin levels in the rat.

The effect of acute administrations of three doses of imipramine (1, 5 and 10 mg/kg s.c.), a widely used tricyclic antidepressant, on extracellular levels of serotonin (5-HT) has been studied by intracerebral microdialysis in raphe nuclei and prefrontal cortex of conscious rats. Imipramine 1 mg/kg s.c. did not change extracellular 5-HT in either raphe nuclei and prefrontal cortex. However, with the dose of 5 mg/kg s.c. imipramine induced in raphe nuclei, a brief increase of extracellular 5-HT followed by a lowering (55-65% basal release) of the neurotransmitter. The same dose of imipramine decreased (60-70% of basal value) extracellular 5-HT in prefrontal cortex. Imipramine 10 mg/kg s.c. significantly increased 5-HT levels in both raphe nuclei (190 +/- 20% above basal value) and prefrontal cortex (280 +/- 15% above basal value). Pretreatment with (-)pindolol (5 mg/kg s.c.), a non-selective 5-HT1A subtype receptor antagonist, 30 min before imipramine 5 mg/kg, modified the effect of the antidepressant: an increase, instead of a decrease, on prefrontal cortex dialysate 5-HT was observed. (-)Pindolol (10 mg/kg s.c.) increased extracellular 5-HT in both raphe nuclei (155 +/- 20% above basal value) and prefrontal cortex (160 +/- 8% above basal value). These data show that acute administration of imipramine modifies extracellular 5-HT at the level of the raphe nuclei and prefrontal cortex. 5-HT1A autoreceptors in the raphe nuclei, which this study suggests to be tonically active, may be stimulated after systemic administration of high doses of imipramine.

Adrenergic beta-Antagonists↗

PubMed1997

AMPA receptors modulate extracellular 5-hydroxytryptamine concentration and metabolism in rat striatum in vivo.

We have investigated the effects of infusing the excitatory amino acid agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on extracellular levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum using in vivo microdialysis. AMPA (50-500 microM) caused a concentration-dependent increase in extracellular 5-HT, while having the converse effect on 5-HIAA. At the highest agonist dose the decrease in dialysate 5-HIAA was followed by a significant increase in this metabolite. Two hundred micromolar 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a competitive non-NMDA glutamate receptor antagonist, reversed the effects of a 100 microM AMPA on dialysate 5-HT and 5-HIAA. Co-infusion of AMPA with tetrodotoxin (TTX) abolished the effects of 100 microM AMPA, but only partially reversed the effect of 500 microM AMPA on 5-HT release. We have also investigated whether AMPA receptor desensitization, a well documented event, plays a role in AMPA receptor modulation of striatal 5-HT release. Diazoxide (500 microM), a drug which prevents AMPA receptor desensitization, failed to augment the effect of 100 microM AMPA on 5-HT release. Diazoxide alone significantly decreased 5-HT release, as did the drug cromakalim (100 microM), probably as a result of their common action as activators of ATP-dependent K+ channels. It is concluded that AMPA receptors play a role in regulating both 5-HT release and metabolism in rat striatum. However, AMPA receptor desensitization does not appear to play a role in this process in this structure.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1996

Hypothalamic paraventricular nucleus involvement in the pressor response to N-methyl-d-aspartic acid in the periaqueductal grey matter.

The aim of this study was to demonstrate paraventricular hypothalamic nucleus (PVN) involvement in the cardiovascular changes induced by N-methyl-d-aspartic acid (NMDA) microinjections at the level of periaqueductal grey (PAG) matter. The study was carried out in anaesthetized rats and the arterial blood pressure monitored by a polygraph. NMDA injections (0.68-6.8 nmol/rat) into the PAG area induced a significant increase in blood pressure. After pretreatment by injection of the NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (2-APV, 0.05-5 nmol/rat) into the PVN, administration of NMDA (0.68 nmol/rat) into the PAG area elicited a decrease, rather than an increase, of blood pressure. We observed a significant reduction of the pressor effect induced by 6.8 nmol/rat NMDA after 2-APV injection into the PVN. 2-APV injection into the dorsomedial hypothalamic nucleus, an area near the PVN, did not modify the increase in blood pressure induced by NMDA in the PAG area. We suggest the existence of a glutamatergic connection between the PAG area and the PVN in the cardiovascular effects of NMDA.

Animals↗

PubMed1996

Selective and non-selective ET antagonists reveal an ETB receptors mediated ET-1-induced behavioural effect in conscious rats.

The injection of endothelin-1 (ET-1) (1 pmol/rat) into the dorsolateral periaqueductal gray (PAG) area of freely moving rats induced rotation along the long axis of the body (barrel-rolling). Preinjection (10 min before) of BQ-788 (an ETB receptor selective antagonist; 5 nmol) or bosentan (an ETA/ETB receptor non-selective antagonist; 10 nmol) to the PAG reduced the behavioral response to ET-1. In contrast, pretreatment with FR139317 (an ETA receptor selective antagonist; 5 nmol) did not affect the ET-1-induced barrel-rolling. These results suggest that barrel-rolling induced by microinjection of ET-1 into the PAG area is predominantly mediated via ETB-like receptors.

Animals↗

PubMed1996

Involvement of nitric oxide in cardiorespiratory regulation in the nucleus tractus solitarii.

The aim of this study was to investigate whether nitric oxide (NO) is involved in cardiorespiratory regulation in the nucleus tractus solitarii (NTS). Unilateral microinjections (50 nl) of the NO-donor, sodium nitroprusside (SNP, 40-100-200 mM), into the NTS of anaesthetized rats elicited dose-dependent apnea (7.3 +/- 2.3 sec; 28.6 +/- 5.7 sec; 35.6 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (8.4 +/- 3.1 mmHg; 18.2 +/- 5.8 mmHg; 25.8 +/- 6.7 mmHg, respectively; n = 6). Similarly, unilateral micro-injections (50 nl) of another NO-donor, 3-morpholinosydnonimine (SIN-1, 20-40-100 mM), also induced apnea (5.1 +/- 2.4 sec; 8.7 +/- 4.3 sec; 26.3 +/- 6.4 sec, respectively; n = 6) and a decrease in arterial blood pressure (6.2 +/- 2.3 mmHg; 11.1 +/- 3.3 mmHg; 18.3 +/- 6.1 mmHg, respectively; n = 6). The SNP- and SIN-1-induced apnea and arterial blood pressure decrease were significantly (p < 0.01) blocked by a 3 min pretreatment with two calcium-channel blockers, diltiazem (0.1 mM) and cobalt (10 mM), while lower doses (diltiazem 0.01 and cobalt 1) were ineffective. Microinjections of diltiazem (0.01 mM) and cobalt (1 mM) alone did not induce any change in basal cardiorespiratory values like diltiazem (0.1 mM) and cobalt (10 mM). These data suggest that NO may be involved in NTS cardiorespiratory regulation via calcium-channel activation.

Animals↗

PubMed1996

Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve.

OBJECTIVE: To investigate the pattern of diastolic abnormalities in patients with systemic sclerosis (SSc) and the relationship between impaired ventricular filling and systolic function. METHODS: Twenty four patients with SSc underwent M-mode and two dimensional echocardiography using echo-Doppler and gated blood pool cardiac angiography, both at rest and after exercise. RESULTS: An impaired diastolic relaxation of the left ventricle was detected in 10 of the 24 patients with SSc. Left ventricular ejection fraction at rest in these 10 patients with impaired ventricular filling did not differ from that in the remaining 14 patients, but eight of the 10 failed to increase their ejection fraction during exercise, compared with two of the 14 with normal ventricular filling (p = 0.003). CONCLUSION: Impaired relaxation of the left ventricle is a recently described feature of scleroderma heart disease. Diastolic dysfunction in SSc could depend on myocardial fibrosis or myocardial ischaemia, or both. It was found to be associated with a defective cardiac functional reserve. However, its prognostic significance remains to be clarified.

Adult↗

PubMed1996

[Cardiopathy in systemic sclerosis].

Cardiac involvement is quite frequent in systemic sclerosis (SSc). From a pathophysiologic point of view, one must differentiate a primary scleroderma heart disease due to pericardial and/or myocardial and/or small coronary intramyocardial vessel involvement from heart disease secondary to either pulmonary interstitial or vascular involvement (pulmonal cor) or to kidney disease (hypertensive myocardial disease). A significant difference emerges when the prevalence of clinically and standard ECG detected cardiac involvement in SSc patients is compared with that registered at autopsy. In the last years, however, Holter ECG, echocardiography, perfusional scintigraphy and ventriculography have reduced such gap, a preclinical scleroderma heart disease being detected by such techniques in quite a high percentage of SSc patients. Asymptomatic SSc patients may be found to present small pericardial effusions and/or either fixed (fibrosis) or reversible (vascular disease) or both types thallium defects or a defective cardiac functional reserve. Both clinically evident scleroderma heart disease and ventricular arrhythmias have a poor prognostic significance. Therefore, a complete cardiological work-up must be periodically carried out in SSc patients. Scleroderma heart disease has long been considered a condition difficult to treat. The detection of diastolic abnormalities and of diastolic failure in SSc patients make us able to understand the therapeutic failure of inotropic agents. Recently, captopril has been shown to improve cardiac function in SSc. It might act either on vascular disease or on fibrosis by affecting the remodelling process of the myocardial wall.

Cardiomyopathies↗

PubMed1995

Metabotropic and ionotropic glutamate receptors mediate opposite effects on periaqueductal gray matter.

Microinjections, into the dorso-lateral periaqueductal gray matter, of N-methyl-D-aspartic acid (NMDA, 0.07-7 nmol/rat) significantly (P < 0.01) increased arterial blood pressure in a dose-related manner. Pretreatment, 5 min before NMDA (7 nmol/rat), in the same area with 2-amino-5-phosphonovaleric acid (2-APV, 5 nmol/rat), a selective antagonist of NMDA receptors, significantly (P < 0.01) reduced NMDA-induced arterial hypertension. trans-(+/-)-1-Amino-1,3-cyclopentanedicarboxylic acid (t-ACPD, 6-30 nmol/rat), an agonist of metabotropic glutamate receptors (mGlu receptors), significantly (P < 0.01) decreased arterial blood pressure when microinjected into the dorsal-lateral periaqueductal gray matter. Pretreatment, 5 min before t-ACPD (30 nmol/rat), in the same area with L-2-amino-3-phosphono-propionate (L-AP-3, 30 nmol/rat), a putative antagonist of the mGlu receptors, was not able to prevent t-ACPD-induced hypotension. Microinjections of L-AP-3 (30 nmol/rat) induced a hypotension similar to the one obtained with t-ACPD at the dose of 6 nmol/rat. From these data we can suggest that mGlu receptors act inversely to the NMDA receptors in the dorso-lateral periaqueductal gray area and that L-AP-3 is a partial agonist rather than an antagonist of mGlu receptors within the periaqueductal gray area.

2-Amino-5-phosphonovalerate↗

PubMed1995

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors modulate dopamine release in rat hippocampus and striatum.

The effects of infusing the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) on the release of dopamine (DA) has been studied in rat hippocampus and striatum in vivo. In hippocampus, AMPA (1-10 microM) produced a dose related increase in dialysate DA, but at 100 microM AMPA a sustained decrease in extracellular DA was observed. However, when samples were collected at 5-min intervals 100 microM AMPA infusion revealed a brief increase in hippocampal dialysate DA. Infusion of 100 microM AMPA and 500 microM diazoxide, which blocks AMPA receptor desensitization, led to a marked increase in extracellular DA, as did diazoxide alone, although to a lesser extent. The AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3,-dione (CNQX; 200 microM) reversed the effect of AMPA and/or diazoxide infusion on dialysate DA and when infused alone, CNQX also decreased hippocampal dialysate DA. AMPA (50-500 microM) increased striatal DA release. The effect of AMPA on extracellular DA was reversed by CNQX (200 microM). Diazoxide infusion caused a decrease in striatal DA release, and this was not affected by CNQX. These data suggest that hippocampal, but not striatal AMPA receptor desensitization may play a role in regulating DA release.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Effects of intravenous digoxin on pulmonary venous and transmitral flows in patients with chronic heart failure of different degrees.

Acute effects of digoxin on diastole were evaluated noninvasively by combining data simultaneously obtained by Doppler echocardiograms (echo-Doppler) of transmitral and pulmonary venous flow curves in 38 patients with dilated and failing hearts, who had been stable for at least 7 days before the study. According to the resting ejection fraction (EF), patients were subdivided into Group 1 (EF < 30%: n = 20, mean EF values 23 +/- 8%) and Group 2 (EF > or = 30%: n = 18, mean EF values 40 +/- 3%). Significant differences were observed at rest between the two groups in both transmitral (shorter deceleration time and isovolumic relaxation time and increased peak E and E/A ratio in Group 1 vs. Group 2) and transpulmonary (reduced systolic forward component and systolic fraction of the flow curves in Group 1 compared with Group 2 and control subjects) parameters. Digoxin (1 mg subdivided into two doses, each infused over a 15-min period with 2 h between the doses) significantly modified the diastolic profile in Group 1 patients in the absence of statistically relevant changes in EF: a significant decrease of transmitral peak E (from 76 +/- 17 to 60 +/- 15 cm/s, p < 0.05) and E/A ratio (from 2.5 +/- 1 to 1.6 +/- 0.6; p < 0.05) and a significant lengthening of deceleration time (from 115 +/- 20 to 160 +/- 18 ms; p < 0.05) were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Involvement of opioid receptors in N-methyl-D-aspartate-induced arterial hypertension in periaqueductal gray matter.

Arterial hypertension induced by microinjections of N-methyl-D-aspartate (NMDA) (2 nmol/rat) into the midbrain periaqueductal gray matter was used to assess the involvement of opioid receptors (mu, delta and kappa) in modulating pressor periaqueductal gray neurons. Groups (n = 5-8) of urethane-anaesthetised rats received, 5 min before NMDA, microinjections of selective opioid receptor antagonists in the periaqueductal gray area and arterial blood pressure was monitored. Pretreatments with naloxone (5 nmol/rat), a non selective mu receptor antagonist, or naltrindole hydrochloride (5 nmol/rat), a selective delta receptor antagonist, significantly (P < 0.05) decreased by 31% and 37%, respectively, NMDA-induced hypertension. The latency for the maximum increase of NMDA-induced hypertension was also significantly (P < 0.05) increased with naloxone. Pretreatment with nor-binaltorphimine (5 nmol/rat), a selective kappa receptor antagonist, only increased the latency of NMDA-induced hypertension. Each opioid antagonist failed per se to alter arterial blood pressure. Microinjection of morphine (13 nmol/rat), a non selective mu receptor agonist, significantly decreased (P < 0.05) by 57.5% NMDA-induced arterial hypertension and this effect was antagonised by naloxone. Combined pretreatments in the periaqueductal gray area with naloxone and the GABAA antagonist bicuculline (2.5 nmol/rat; 5 min before naloxone) antagonised the effect of naloxone on NMDA-induced hypertension. In contrast, bicuculline significantly (P < 0.05) potentiated morphine-induced decrease of NMDA hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1995

Effects of L-name on endothelin-1-induced barrel-rolling in periaqueductal gray area of rats.

The injection of endothelin-1 (ET-1) into the dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 pmol/rat induced rotation along the long axis of the body (barrel-rolling). The pretreatment of this area with L-NAME (N omega-nitro-L-arginine methyl ester, 1 mumol/rat), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) biosynthesis, significantly (p < 0.01) potentiated the duration of the ET-1-induced barrel-rolling. Pretreatment of the PAG area with L-arginine (1 mumol/rat), a precursor of NO, significantly (p < 0.01) decreased the ET-1-induced effects. These preliminary data indicate that the L-arginine-NO pathway exerts a functional antagonism on ET-1 induced barrel-rolling at the level of the PAG area.

Animals↗

PubMed1995

Behavioural effects induced by microinjection of L-BOAA into the ventrolateral PAG matter of the mouse.

L-BOAA (1 microgram/mouse), microinjected into the ventrolateral periaqueductal gray (PAG) matter, induced a strong reaction of forward avoidance (running) for 20-30 s in 18% of the mice and immobility for 7 +/- 2 min in 72% of the mice from a total of 68 treated animals. Effects were also observed for grooming and clonus in 6% and 4% of the mice, respectively. Duration of L-BOAA-induced immobility was significantly (p < 0.05) reduced by a pretreatment with CNQX (0.5 microgram/mouse), a selective antagonist of AMPA glutamergic subtype receptors, but not by a pretreatment with 2-APV (0.5 microgram/mouse), a selective antagonist of NMDA glutamergic subtype receptors, nor by 2-AP3 (0.5 microgram/mouse), a weak antagonist of metabotropic glutamergic subtype receptors. AMPA (0.05 microgram/mouse), also microinjected into ventrolateral PAG, induced the same pattern of behavioural effects as L-BOAA. Forward avoidance, grooming, and clonus induced by L-BOAA or AMPA were also significantly antagonised by a pretreatment with CNQX (data not shown).

Amino Acids, Diamino↗

PubMed1995

Endothelin-1 in rat periaqueductal gray area induces hypertension via glutamatergic receptors.

We investigated the possible relationship between endothelin-1 injection into the dorsolateral periaqueductal gray area and the glutamatergic system in the control of cardiovascular function. Endothelin-1 was injected into the dorsolateral periaqueductal gray area of freely moving rats at doses ranging from 0.1 to 10 pmol. Endothelin-1 increased arterial blood pressure (from 7.0 +/- 1.6 to 55.0 +/- 4.1 mm Hg, mean +/- SEM) in a dose-dependent manner and induced characteristic behavioral changes such as longitudinal rolling of the body (barrel-rolling). DL-2-Amino-5-phosphonovaleric acid and (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[D-alpha] cyclohepten-5,10-imine hydrogen maleate, both selective N-methyl-D-aspartate excitatory amino acid receptor antagonists, but not 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, significantly decreased endothelin-1-induced cardiovascular and behavioral changes (P < .01). Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, also prevented these effects. We propose that the glutamatergic system may exert, via N-methyl-D-aspartate receptors, a significant influence on endothelin-1-induced cardiovascular and behavioral effects after its injection into the periaqueductal area.

Animals↗

PubMed1994

N-methyl-d-aspartate receptors modulate extracellular dopamine concentration and metabolism in rat hippocampus and striatum in vivo.

The effects of infusing N-methyl-D-aspartate (NMDA), and the specific NMDA receptor antagonist D-2-amino-5-phosphono-propionic acid (D-AP5) into rat hippocampus and striatum on extracellular dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were studied using intracerebral microdialysis. In striatum NMDA increased DA extracellularly in a concentration-dependent manner. Against a 10 microM concentration of NMDA the increase in striatal DA was opposed by D-AP5 (10 microM in all experiments), which when infused alone significantly reduced DA concentration. Infusion of NMDA altered DOPAC level in a complex manner, with 10 microM concentration causing a significant increase 2 h after infusion, while 100 microM NMDA caused a transient decrease in the metabolite. None of treatments altered striatal dialysate HVA. In hippocampus NMDA infusion decreased dialysate DA in a concentration-dependent manner, and the decrease caused by 10 microM NMDA was reversed by D-AP5. When given alone the antagonist was without effect. NMDA infusion elevated hippocampal dialysate DOPAC and HVA, while HVA was decreased following D-AP5 infusion. These data indicate that DA release is regionally controlled by excitatory amino acids, but in differential manner.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Evidence that arcaine increases the N-methyl-D-aspartate-induced cardiovascular effects into the periaqueductal gray area of anesthetized rats.

In the present study the influence of arcaine (0.01-1 microgram/rat), an in vitro putative non-competitive antagonist of the NMDA receptors, on cardiovascular changes induced by intracerebral administration of N-methyl-D-aspartate (NMDA) (0.1 microgram/rat) has been evaluated. Both NMDA and arcaine were microinjected into the periaqueductal gray (PAG) area of anesthetized rats. Arcaine did not decrease NMDA-induced arterial hypertension and tachycardia, but, in a dose-related manner, increased the NMDA-induced cardiovascular effects. Moreover, treatment with arcaine was not able per se to modify arterial blood pressure and heart rate basal values. Although updated in vitro reports indicate arcaine as a blocker of the NMDA receptors by an open channel mechanism, our in vivo results, at the level of the PAG area, show this not to be true. Indeed the drug may facilitate NMDA receptor activation.

2-Amino-5-phosphonovalerate↗