Biomedical subjects

S Maione

Publications and source records attributed to S Maione.

At least 19 recordsLinked to original sources

PubMed2001

Metabotropic and NMDA glutamate receptors participate in the cannabinoid-induced antinociception.

The purpose of this study was to evaluate the possible contribution of metabotropic glutamate receptors (mGluRs) to cannabinoid-induced antinociception in the periaqueductal grey (PAG) matter of rats. Intra-PAG microinjection of WIN 55,212-2, a cannabinoid receptor agonist, increased the latency of the nociceptive reaction (NR) in a dose-dependent fashion in the plantar test. This effect was prevented by pretreatment with SR141716A, a selective antagonist of CB1 receptors. When injected alone, SR141716A produced, with the highest dosage used, a significant reduction in the latency of the NR. CPCCOEt, a selective mGlu1 receptor antagonist, was unable to prevent the analgesia produced by WIN 55,212-2. On the contrary, MPEP, a selective mGlu5 receptor antagonist, completely antagonized the effect of WIN 55,212-2. However, the analgesia induced by CHPG, a selective mGlu5 receptor agonist, was blocked by MPEP but not by SR141716A. When injected alone, CPCOOEt produced no effect, whereas MPEP produced, with the highest dosage used, a significant reduction in the latency of the NR. These data emphasize that mGlu5 receptors, but not mGluR1, may modulate nociception in the PAG. Similarly, a pretreatment with either 2-(S)-alpha-EGlu or (RS)-alpha-MSOP, selective antagonists for group II and III mGluRs, respectively, prevented the WIN 55,212-2-induced analgesia. When the higher dosage of (RS)-alpha-MSOP was used a decrease in the latency of the NR was observed. This was not the case for 2-(S)-alpha-EGlu. Pretreatment with DL-AP5, a selective antagonist of N-methyl-D-aspartate (NMDA) receptors, blocked the effect of WIN 55,212-2, and by increasing the dosage strongly reduced per se the latency of the NR. This study suggests that endogenous glutamate could tonically modulate nociception through mGlu and NMDA receptors in the PAG matter. In particular, the physiological stimulation of these receptors seems to be required for the cannabinoid-induced analgesia in this midbrain area.

Analgesics↗

PubMed2000

Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception.

The role played by periaqueductal gray (PAG) matter metabotropic glutamate receptors (mGluRs) in the modulation of persistent noxious stimulation was investigated in mice. The formalin test was used as a model of persistent pain. Intra-PAG microinjections of (S)-3, 5-DHPG (25 and 50 nmol/mouse) and L-CCG-I (30 and 60 nmol/mouse), agonists of group I and group II mGluRs, respectively, decreased the nociceptive response (-92+/-6% and -89+/-8%, respectively) during the late phase. No change of the early nociceptive phase was observed after (S)-3,5-DHPG or L-CCG-I treatments. These effects were antagonized by a pretreatment with CPCCOEt (40 nmol/mouse) and (2S)-alpha-EGlu (30 nmol/mouse). CPCCOEt is a selective antagonist of group I mGlu receptors, while (2S)-alpha-EGlu is an antagonist of group II. Intra-PAG microinjections of L-SOP (60 and 120 nmol/mouse), a selective agonist of group III mGluRs, induced an increase of the nociceptive response (+95+/-7%) during the late hyperalgesic phase. (R,S)-alpha-M-SOP (70 nmol/mouse), a selective antagonist of group III mGluRs, completely antagonized the L-SOP-induced effect. These results show that PAG mGluRs participate in modulating the late hyperalgesic behaviours induced by formalin. It seems, therefore, possible that group I and group II mGluRs positively modulate PAG antinociceptive descending pathway following a persistent noxious stimulation, while group III mGluRs modulate it negatively.

Animals↗

PubMed2000

Effects of persistent nociception on periaqueductal gray glycine release.

Glycine is a candidate nociception inhibitory transmitter in specific brain regions, like for example the spinal cord, the thalamic nuclei and the periaqueductal gray matter. However, quantitative changes in glycine released in these brain regions during peripheral inflammation episodes have not been characterized in awake animals. To address this issue, an in vivo microdialysis study was carried out in freely moving rats in order to analyse periaqueductal gray matter extracellular glycine concentration following unilateral formalin injection into the dorsal skin of the right hind-paw. The extracellular concentration of glutamine was also evaluated in order to analyse whether or not a non-neurotransmitter amino acid was equally modified. Intra-periaqueductal gray matter tetrodotoxin perfusion reduced extracellular glycine concentration (-44+/-5%), but did not change the glutamine dialysate values. Peripheral injection of formalin reduced the glycine release during the early phase (-62+/-8%) and the late phase (-36+/-6%) of hyperalgesia, although not during the analgesic period. Perfusion with naloxone (300microM) neither prevented the formalin-induced decreases in extacellular glycine concentration, nor modified the perfusate basal values of glycine and glutamine. These results show that, contrary to what has been recognized on the interactive role of opioids and GABA into the periaqueductal gray matter (i.e. opioid disinhibition), endogenous opioids seem not to modulate the activity of glycinergic neurons in the same midbrain area. In the light of these preliminary data, it is reasonable to suppose that GABA and glycine are probably not co-released at the level of periaqueductal gray matter of the rat.

Animals↗

PubMed2000

Right ventricular diastolic abnormalities in systemic sclerosis. Relation to left ventricular involvement and pulmonary hypertension.

OBJECTIVES: To investigate right ventricular diastolic function in systemic sclerosis (SSc) and its relation to clinical features of the disease. METHODS: Seventy seven unselected SSc patients and 33 healthy subjects were submitted to echocardiography and echo Doppler study to assess left and right systolic as well diastolic function and to estimate maximal arterial systolic pulmonary pressure (PAP). In addition, the patients were investigated to define the SSc subset and the extent of skin and internal organ involvement. RESULTS: An abnormal right ventricular filling, as expressed by an inverted tricuspidal (Tr) E/A ratio (Tr E/A ratio <1), was detected in 31 of the 77 SSc patients (40%) and in 0 of the 36 controls ( p<0.001 ). All the 31 patients with an inverted Tr E/A ratio were found to have a PAP > 30 mm Hg. Twenty resulted to have an inverted mitral (Mit) E/A ratio (Mit E/A ratio <1), indicating an abnormal left ventricular filling. In multiple regression analysis, Tr E/A ratio resulted to be independently correlated to both PAP (r= -0.35;p<0. 003) and Mit E/A ratio (r=0.39;p<0.001). CONCLUSIONS: This study points out an impaired right ventricular filling in a significant percentage of SSc patients whatever the subset. This alteration is independently correlated to both PAP and left ventricular filling abnormalities.

Adult↗

PubMed1999

Periaqueductal gray matter glutamate and GABA decrease following subcutaneous formalin injection in rat.

Glutamate and GABA are important nociception modulating transmitters in specific brain regions, i.e. the spinal cord, the thalamic nuclei and the periaqueductal gray (PAG). However, quantitative and topographical changes in glutamate and GABA release in these brain regions during peripheral inflammation episodes have not been characterized in awake animals. To address this issue, an in vivo microdialysis study was carried out in freely moving rats in order to analyze PAG extracellular glutamate and GABA concentrations following unilateral formalin injection into the dorsal skin of the right hind-paw. Both glutamate and GABA release decreased after the injection of formalin during phase I and phase II of hyperalgesia. Because naloxone prevented the decrease of GABA and glutamate release induced by formalin, this study shows that, in vivo, a nociceptive stimulation may activate opioidergic fibres into the PAG. The increased release of endogenous opioids may, in turn, inhibit the activity of the GABAergic neurons (i.e. opioid disinhibition). Formalin injection also decreased extracellular glutamate concentration. However, we found that intra-PAG perfusion with tetrodotoxin only decreased GABA, but not glutamate dialysate values. Although it should be reasonable to speculate that opioids also inhibit glutamate fibres, further investigation is needed to clarify whether or not the dialysate glutamate we measured reflects change in the metabolism or neurotransmitter pool of this amino acid.

Analysis of Variance↗

PubMed1998

Role of vasopressin on excitatory amino acids mediated pressor responses in the periaqueductal gray area.

In order to evaluate the role played by vasopressin on pressor responses elicited by stimulation of the periaqueductal gray (PAG) area by excitatory amino acids we carried out in vivo studies in genetically vasopressin deficient rats (Brattleboro). Microinjections of 1-glutamic acid (glutamate, 0.6 to 60 nmol/rat) or N-methyl-d-aspartic acid (NMDA, 0.07 to 7 nmol/rat) into the PAG area of freely moving Brattleboro rats induced increases of arterial blood pressure values significantly lower than those obtained in Long Evans rats (control) (glutamate in Brattleboro rats: from +2+/-1 mmHg to 16+/-3 mmHg; glutamate in Long Evans rats: from +16+/-2 mmHg to +36+/-4 mmHg; NMDA in Brattleboro rats: from +5+/-2 mmHg to +34 +/-8 mmHg; NMDA in Long Evans rats: from +18+/-7 mmHg to 80+/-9 mmHg; n=5). Similarly, in anaesthetized Brattleboro rats (urethane 1.2 g/kg i.p.) pressor responses to NMDA microinjections (0.7 nmol/rat) into the PAG area were significantly lower than in Long Evans rats (controls) (+15+/-3 mmHg vs +24+/-4 mmHg). In Long Evans rats NMDA injection also reversed blood pressure decrease induced by ganglionic blocker, hexamethonium and/or losartan (3 mg/kg i.v.), an AT1 receptor antagonist. In Brattleboro rats, NMDA injection did not reverse blood pressure decreases induced by hexamethonium (5 mg/kg i.v.). Moreover, hexamethonium induced blood pressure decrease was not reversed by acetylcholine injection (137 nmol/rat) into the PAG area of anaesthetized Long Evans rats, but if injected before hexamethonium, acetylcholine was able to increase blood pressure (+25+/-3 mmHg). Our results document: i) the importance of the PAG area in the control of cardiovascular system; ii) the involvement of excitatory amino acids in the neural control of vasopressin release; iii) the close relationship between glutamate and vasopressin in the central blood pressure regulation.

Acetylcholine↗

PubMed1998

Metabotropic glutamate receptors modulate serotonin release in the rat periaqueductal gray matter.

The role of metabotropic (mGluRs) and N-methyl-D-aspartate (NMDA) glutamate receptors on 5-hydroxytryptamine (5-HT) release has been studied in rat periaqueductal gray (PAG) matter by using in vivo microdialysis. (1S,3R)-aminocyclopentane- 1,3-dicarboxylic acid [(IS,3R)-ACPD; 0.5 or 1 mM], a group I/group II mGluRs agonist, increased the dialysate 5-HT concentration. (2S)-alpha-ethylglutamic acid (EGlu; 1 mM), an antagonist of group II mGluRs, but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 mM), an antagonist of group I mGluRs, antagonized the 1S,3R-ACPD-induced effect. (S)-3,5-dihydroxyphenylglycine (DHPG; 0.5 and 1 mM), an agonist of group I mGluRs, did not modify dialysate 5-HT. (2S, 3S, 4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-I; 0.5 and I mM), an agonist of group II mGluRs, increased extracellular 5-HT. This effect was antagonized by EGlu. Similarly, L-serine-O-phosphate (L-SOP; 1 and 10 mM), an agonist of group III mGluRs, increased extracellular 5-HT and this effect was antagonized by (RS)-(alpha-methylserine O-phosphate (M-SOP; 1 mM), an antagonist of group III mGluRs. Out of the several N-methylD-aspartate concentrations used (NMDA; 10, 50, 100, 500 and 1000 microM) only the 50 microM infusion significantly decreased dialysate 5-HT. The GABA(A) receptor agonist, bicuculline (30 microM), increased 5-HT release on its own and antagonized the decrease caused by the opiate antagonist, naloxone (2 mM), as well as the increases caused by CCG-I or L-SOP. These data show that stimulation of PAG's group II/group II mGluRs increases 5-HT release, while stimulation of NMDA glutamate receptors may decrease it. We speculate that glutamate does not modulate 5-HT release in the PAG directly, but via activation of tonically active GABAergic interneurons.

Animals↗

PubMed1998

Characterisation of mGluRs which modulate nociception in the PAG of the mouse.

The contribution of metabotropic glutamate receptors (mGluRs) to the modulation of nociception by the periaqueductal gray (PAG) matter was investigated in mice. Intra-PAG microinjection of (IS,3R)-ACPD, an agonist of groups I and II mGluRs, as well as (S)-3,5-DHPG, a selective agonist of group I mGluRs, increased the latency of the nociceptive reaction (NR) in the hot plate test. (RS)-AIDA, an antagonist of group I mGluRs, antagonized the effect of (S)-3,5-DHPG, but changed the effect induced by (1S,3R)-ACPD in that a decrease in the latency for the NR could now be observed. L-CCG-I and L-SOP, which are agonists of groups II and III mGluRs respectively, decreased the latency of the NR. (2S)-alpha-EGlu and (RS)-alpha-MSOP, which are antagonists of groups II and III mGluRs, respectively, antagonized the effect of L-CCG-I and L-SOP. (RS)-AIDA and (RS)-alpha-MSOP alone decreased and increased, respectively, the latency of the NR with the highest doses used. (2S)-alpha-EGlu alone did not change significantly the latency of the NR. Intra-PAG microinjection of LH, an agonist of ionotropic glutamate receptors, induced a dose-dependent analgesia which was blocked by pretreatment with DL-AP5, a selective antagonist of NMDA receptors. No mGluRs antagonists were able to prevent LH-induced analgesia. These results emphasize the possible involvement of mGluRs in the modulation of nociception. It seems that activation of group I mGluRs potentiates, while groups II and III mGluRs decrease, the activity of the PAG for the modulation of nociception.

2-Amino-5-phosphonovalerate↗

PubMed1998

Effects of diethylenetriamine on NMDA-induced increase of blood pressure in rats.

We investigated the effects of three doses of diethylenetriamine (DET; 0.1-1-10 nmol/rat), putative ligand at the polyamine site on NMDA receptors, on blood pressure increase induced by N-methyl-D-aspartate (NMDA, 2 nmol/rat) microinjected at the periaqueductal gray (PAG) matter. Said doses of DET did not modify basal arterial blood pressure. Pretreatment with DET, depending on the dose used, either potentiated (DET, 0.1 nmol/rat), reduced (DET, 1 nmol/rat) the NMDA effects or left them unchanged (DET, 10 nmol/rat). DET 10 nmol/rat, microinjected 5 min before spermidine (SPD, 0.02-2 nmol/rat), significantly antagonized SPD modulation on the NMDA-induced pressor changes. These data, in agreement with the functional findings in vitro, suggest that also in vivo DET has pharmacological activities quite different from a pure antagonist but shows multiple actions on the NMDA receptors.

Analysis of Variance↗

PubMed1998

The role of A3 adenosine receptors in central regulation of arterial blood pressure.

1. Pharmacological studies have suggested that A3 receptors are present on central neurons. Recently this adenosine receptor subtype has been identified in the rat and its presence in the central nervous system has been confirmed. 2. In this study we investigated the effects of acute intracerebroventricular (i.c.v.) injections of N6-2-(4-aminophenyl)-ethyladenosine (APNEA), a non-selective A3 adenosine receptor agonist, on arterial blood pressure (ABP) and heart rate (HR), after treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of A1 adenosine receptors. 3. Anaesthetized rats, after DPCPX (12 microg(-1) kg i.c.v.), were treated with APNEA (0.4-4 microg kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arterial blood pressure without a change in heart rate. APNEA also induced hypotensive responses after i.c.v. pretreatment with aminophylline, at a dose of 20 microg kg(-1). In contrast, pretreatment 48 h before, with 4 microg kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effect induced by APNEA. Administration of APNEA at a higher dose (20 microg kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mmHg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1). Transection of the spinal cord abolished this significant fall in ABP, but not the decrease of HR. 4. These results suggest that a population of A3-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.

Animals↗

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↗