[The association of cholesterol crystals and non-culprit plaque characteristics in AMI patients: an OCT study].

Objective: To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment. Methods: This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups. Results: A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque (OR=1.583, 95%CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture (OR=1.632, 95%CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions: Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

[Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis].

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

[Role of CXCL12-CXCR4/CXCR7 signal axis in liver regeneration and liver fibrosis].

Chemokine CXC ligand 12 (CXCL12)-chemokine receptor 4 (CXCR4) signal axis is involved in the regulation of liver injury repair and the occurrence and development of liver fibrosis. In case of acute and chronic liver injury, the expression of CXCL12 is up-regulated to collect CXCR4-positive immune cells to migrate to the liver. The CXCL12-CXCR4 pathway participates in the occurrence of liver fibrosis by promoting the activation and proliferation of hepatic stellate cells. The emergence of small molecule inhibitors of CXCR4 makes this receptor an attractive target for anti-fibrosis therapy. At present, CXCR4 has been tried as an anti-fibrosis treatment targets for fibrosis of various organs, including pulmonary fibrosis and chronic pancreatitis. However, some studies have shown that simply blocking the CXCL12/CXCR4 axis cannot improve liver fibrosis and even aggravate liver injury. In recent years, with the discovery and understanding of CXCR7, another receptor of CXCR12, the counteracting role of CXCR4-promoting fibrosis pathway and CXCR7-promoting regeneration pathway in liver regeneration and liver fibrosis has been interpreted. Therefore, a full understanding of the regulatory mechanism of CXCL12-CXCR4/CXCR7 pathway, the development of corresponding targeted therapy research for liver disease, and the rebalancing of CXCR4 and CXCR7 are expected to become a new strategy for the liver fibrosis therapy.

[Association between interleukin-17A and 17F single nucleotide polymorphisms and knee osteoarthritis].

Objective: To investigate the association between single nucleotide polymorphisms (SNP) of IL-17A (rs2275913) and IL-17F (rs763780) genes and susceptibility to knee osteoarthritis (KOA) in Chinese Han and Tibetan populations. Methods: A case-control study was conducted. Total of 122 Han KOA patients and 124 Han healthy controls and 76 Tibetan KOA patients and 68 Tibetan healthy controls in Qinghai Province were selected between 2015 and 2017. SNP typing was performed on four groups of rs2275913 and rs763780 polymorphisms by polymerease chain reaction (PCR)-sequencing to detect IL-17A and IL-17 F genotype frequencies and allele frequencies. The t test was used to compare data between groups. Results: The genotype AA frequency of IL-17A (rs2275913) was significantly different between the Han KOA and the control group (OR=2.625, P=0.016). Compared with the frequency of allele A in healthy control group, the allele A frequency in Han KOA group was significantly higher(OR=1.445, P=0.047); the genotype frequency of IL-17A,however,was comparable between the KOA and the healthy control in Tibetan population (OR=1.696, 1.355, both P>0.05); there were also not difference in the IL-17F (rs763780) genotype frequency and allele frequency between the Han KOA and Tibetan KOA groups and two control groups,respectively (OR=1.346, 1.126, both P>0.05). Conclusion: It is highly likely that the pathogenesis of KOA in Chinese Han population is positively related to the genotype AA and allele A of IL-17A (rs2275913).

Double-balloon catheter versus prostaglandin E2 for cervical ripening and labour induction: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour has become an increasingly common procedure. Ripening methods, including mechanical devices and pharmacological agents, improve the success rate of labour induction. OBJECTIVE: To compare the efficacy and safety of the double-balloon catheter with prostaglandin E2 agents used for labour induction. SEARCH STRATEGY: We searched electronic sources from MEDLINE, Embase and Web of Science, the Cochrane Library Database of Systematic Reviews, and ClinicalTrials.gov website. SELECTION CRITERIA: Only randomised controlled trials comparing the PGE2 agents with the double-balloon catheter for cervical ripening and labour induction in women with unfavourable cervices were included in the analysis. DATA COLLECTION AND ANALYSIS: The main outcomes included the vaginal delivery rate within 24 hours and risk of caesarean section. We calculated relative risks and mean differences using fixed- and random-effects models. MAIN RESULTS: Nine studies (1866 patients) were included in this systematic review. Both the double-balloon catheter and PGE2 agents were comparable with regard to rate of caesarean section (RR 0.92; 95% CI 0.79, 1.07), vaginal delivery within 24 hours (RR 0.95; 95% CI 0.78, 1.16) and maternal adverse events, but the risk of excessive uterine activity (RR 10.02; 95% CI 3.99, 25.17) and need for neonatal intensive care unit admissions (RR 1.31; 95% CI 1.01, 1.69) were significantly increased in women who received PGE2 agents. CONCLUSIONS: The double-balloon catheter demonstrated greater safety and cost-effectiveness than PGE2 agents for cervical ripening and labour induction. The efficacy profiles of both methods were similar. TWEETABLE ABSTRACT: Double-balloon catheter versus prostaglandin E2 for cervical ripening and labour induction.

Serum vitamin D level is associated with disease severity and response to ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in various autoimmune and liver diseases. AIM: To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA). METHODS: Consecutive PBC patients were retrospectively reviewed. 25-hydroxyvitamin D [25(OH)D] levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris-I and Barcelona criteria. Logistic regressions were performed to identify the treatment response-associated parameters. RESULTS: Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris-I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02-15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023). CONCLUSIONS: 25(OH)D level is associated with biochemical and histological features in PBC. Pre-treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.

Pre- and postsynaptic GABA(B) receptors modulate rapid neurotransmission from suprachiasmatic nucleus to parvocellular hypothalamic paraventricular nucleus neurons.

The suprachiasmatic nucleus (SCN), the dominant circadian pacemaker in mammalian brain, sends axonal projections to the hypothalamic paraventricular nucleus (PVN), a composite of magno- and parvocellular neurons. This neural network likely offers SCN output neurons a means to entrain diurnal rhythmicity in various autonomic and neuroendocrine functions. Earlier investigations using patch-clamp recordings in slice preparations have suggested differential innervation by SCN efferents to magnocellular versus parvocellular PVN cells. In magnocellular PVN, cells respond to focal electrical stimulation in SCN with a GABA(A) receptor-mediated postsynaptic inhibition whose magnitude can be modulated by presynaptic GABA(B) receptors. By contrast, SCN-evoked responses in parvocellular PVN neurons typically involve both GABA(A)- and glutamate-receptor-mediated components. In the present patch-clamp study, 69/85 periventricular parvocellular PVN cells displayed SCN-evoked inhibitory and/or excitatory postsynaptic currents (IPSCs; EPSCs). In the presence of selective receptor antagonists, we sought evidence for their modulation by GABA acting at pre- and/or postsynaptic GABA(B) receptors. Cells responded to bath-applied baclofen (5-10 microM) with a tetrodotoxin-resistant membrane hyperpolarization associated with a reduction in input resistance and/or outward current, due to increase in a potassium conductance, blockable with 2-hydroxysaclofen (300 microM). At 1 microM where baclofen had no significant postsynaptic effect, evidence of activation of presynaptic GABA(B) receptors included reduction in SCN-evoked IPSCs and EPSCs with no change in their kinetics, and paired-pulse depression that was sensitive to both baclofen and saclofen. Baclofen also induced significant reductions in frequency but not amplitudes of miniature IPSCs and EPSCs. These observations suggest that levels of synaptically released GABA from the terminals of SCN output neurons can influence the relative contribution of pre- versus postsynaptic GABA(B) receptors in modulating both excitatory and inhibitory SCN innervation to parvocellular PVN neurons.

Glutamate and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular neurons.

We used patch-clamp recordings in slice preparations from Sprague-Dawley rats to evaluate responses of 20 spinal-projecting neurons in the dorsal paraventricular nucleus (PVN) to electrical stimulation in suprachiasmatic nucleus (SCN). Neurons containing a retrograde label transported from the thoracic (T(1)-T(4)) intermediolateral column displayed three intrinsic properties that collectively allowed distinction from neighboring parvocellular or magnocellular cells: a low-input resistance, a hyperpolarization-activated time-dependent inward rectification, and a low-threshold calcium conductance. Twelve of fifteen cells tested responded to electrical stimulation in SCN. All of 10 cells tested in media containing 2,3,-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (5 microM) and D(-)-2-amino-5-phosphonopentanoic acid (20 microM) responded with constant latency (11.4 +/- 0.7 ms) inhibitory postsynaptic potentials, able to follow 20- to 50-Hz stimulation and blockable with bicuculline (20 microM). By contrast, all eight cells tested in the presence of bicuculline demonstrated constant latency (9.8 +/- 0.6 ms) excitatory postsynaptic potentials that followed at 20-50 Hz and featured both non-N-methyl-D-aspartate (NMDA) and NMDA receptor-mediated components. We conclude that both GABAergic and glutamatergic neurons in SCN project directly to spinal-projecting neurons in the dorsal PVN.

GABA(B) presynaptically modulates suprachiasmatic input to hypothalamic paraventricular magnocellular neurons.

This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABA(B) receptor activation on GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular nucleus magnocellular neurons evoked by electrical stimulation in the suprachiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1-10 microM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 microM; 3/3 cells). IPSCs displayed paired-pulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but neither altered resting membrane conductances or IPSC time constants of decay. Baclofen induced a significant dose-dependent (1-100 microM) reduction in frequency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reversible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persisted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, implying that these GABA(B) receptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K(+) channels and L-type Ca(2+) channels. Thus pre- and postsynaptic GABA(B) and GABA(A) receptors participate in SCN entrainment of paraventricular neurosecretory neurons.

Neurones in the supraoptic nucleus of the rat are regulated by a projection from the suprachiasmatic nucleus.

1. In the rat, projections from the suprachiasmatic nucleus (SCN) to the supraoptic nucleus (SON) of the hypothalamus were characterized in vivo using extracellular recordings and in slice preparations using both extracellular and whole-cell patch clamp recording. 2. Of 117 magnocellular neurones recorded in the SON in vivo, fifteen (13%) displayed a short latency excitation, sixty-eight (58%) a short latency inhibition, six (5%) were unresponsive and twenty-eight (24%) gave long latency responses following SCN stimulation. 3. The responses of putative vasopressin cells in the SON to SCN stimulation in vivo (4 out of 61 cells, 7% excited; 49 out of 61 cells, 80% inhibited) were significantly different from those of putative oxytocin cells (10 out of 50 cells, 20% excited and 16 out of 50 cells, 32% inhibited; P < 0.02, test for differences between proportions). 4. Recordings in vitro using patch technology in whole-cell mode showed both inward and outward currents in SON cells at holding potentials near resting membrane potential following stimulation of the SCN region. The outward currents could be blocked by bicuculline (10 microM; n = 7) and the inward currents were blocked by the non-NMDA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (5 microM; n = 4). 5. We conclude that there is a strong projection from the SCN to the SON with both inhibitory (GABAergic) and excitatory (glutamatergic) components which may regulate the daily changes in neurohypophysial hormone secretion.

Electrophysiological evidence for retinal projections to the hypothalamic supraoptic nucleus and its perinuclear zone.

Secretion of vasopressin (VP) and oxytocin (OT) displays a daily rhythm. Using electrophysiological methods, we investigated the projections from the optic nerve to the supraoptic nucleus (SON) and its perinuclear zone (PNZ) which might underlie the rhythm. Extracellular recordings were made from magnocellular cells in the SON and its PNZ in 22 urethane-anaesthetized female Wistar rats while stimulating the optic nerve. The responses of magnocellular and PNZ cells were classified as orthodromic excitatory (OD+) or inhibitory (OD-) after creating peri-stimulus time histograms (PSTHs). Twenty-six of 73 (35.6%) VP and OT cells and 16 of 42 (38.1%) PNZ cells were excited by optic nerve stimulation. PNZ cells displayed both short (for 7 cells 30 ms or less) and long (> 60 ms) latency responses. Most (6/7) short latency responses had a short duration but longer latency responses were longer. No magnocellular cells showed responses with both short latency and short duration. Short latency responses with a short duration probably reflect direct monosynaptic inputs whereas longer latency responses with longer duration may reflect complex inputs. Thus the retina projects to the PNZ and to the SON but the PNZ receives a stronger direct input. Such projections might provide a light-related input to SON cells and suggest a role for the PNZ in this input.

Osmotic modulation in glutamatergic excitatory synaptic inputs to neurons in the supraoptic nucleus of rat hypothalamus in vitro.

To clarify influence of osmotic stimulation on the excitatory synaptic inputs to the neurosecretory cells of the supraoptic nucleus (SON), the blind patch technique was used in rat hypothalamic slice preparations. Stable whole-cell recordings were made from 22 neurons in the SON. To observe spontaneous excitatory postsynaptic currents (sEPSCs) in the SON neurons, membrane potentials were clamped between -50 and -90mV. The effects of hypertonic stimulation on the frequency of the sEPSCs were tested in 18 SON neurons. Bath application of mannitol 30 or 60 mM increased the frequency of the sEPSCs. During the application of mannitol (60 mM), the frequency of the sEPSCs increased in 12 of 15 neurons without a change in amplitude. Hypertonic stimulation with NaCl (30 mM) had similar effects to that of mannitol. The increased frequency of miniature EPSCs (mEPSCs) during mannitol application persisted in the presence of TTX in all 8 SON neurons tested with no change in amplitude. Both the non-NMDA antagonist CNQX at 10-30 microM (n = 6) and the non-selective glutamate antagonist kynurenic acid at 1 mM (n = 3) almost completely blocked the EPSCs while the NMDA antagonist AP-5 at 10 microM had no effect on the frequency of the EPSCs in the 4 neurons tested. During application of CNQX, mannitol (60 mM) was added to the perfusion medium in 3 SON neurons. Under these conditions, mannitol had no effect on the frequency of EPSCs. We conclude that hypertonic stimulation directly influences glutamatergic inputs to the neurosecretory cells of the SON by an action on the presynaptic terminals and enhances the excitatory synaptic events.

Synaptic input from the retina to the suprachiasmatic nucleus changes with the light-dark cycle in the Syrian hamster.

1. Single cell extracellular recordings were made from the suprachiasmatic nucleus (SCN) in urethane-anaesthetized Syrian hamsters at different times of the light-dark cycle. Peristimulus time histograms (PSTHs) were created following stimulation of the optic nerve. 2. Both short-latency (< 50 ms) and long-latency (> 50 ms) excitatory responses were seen. Almost all inhibitory responses had a short latency. 3. A total of 288 SCN neurones were recorded. Taking all types of response together, 55 (36.9%) of the 149 neurones tested in the dark period responded to optic nerve stimulation while only 23 (16.6%) of the 139 neurones tested in the light period responded. The difference between the proportion of all responsive and non-responsive neurones in the dark and light periods was highly significant (P < 0.01, Fisher's exact probability test). The difference in the proportion of excitatory responses was also significant (P < 0.01). 4. During the dark period, the mean spontaneous firing rate (5.00 +/- 0.88 spikes s-1; mean +/- S.E.M., n = 55) of the responsive cells was significantly higher than that of the non-responsive cells (2.65 +/- 0.33 spikes s-1; mean +/- S.E.M., n = 74; P < 0.01; Student's unpaired t test). 5. Injection of APV (20 mM, 2 microliters, I.C.V.; n = 6), an antagonist for the NMDA receptor, or CNQX (10 mM, 2 microliters, I.C.V.; n = 5), an antagonist of the non-NMDA receptor, significantly reduced the responses of all the neurones tested. 6. We conclude that there is daily variation in the firing of SCN neurones in vivo and the variation is restricted to those cells receiving optic nerve inputs. The change in the responsiveness of the SCN to optic nerve stimulation at different times of day suggests that there is a rapidly changing cycle of synaptic function in the SCN. The action of the antagonists suggests that the excitatory retinal projections to the SCN which show this variation are mediated by glutamate and that both NMDA and non-NMDA receptors are involved.

Cardiovascular system related peptides and hypothalamic neurons.

The hypothalamus is known to be an integrative site of cardiovascular, endocrine and autonomic functions. Our previous studies, using extracellular, intracellular and/or whole cell patch-clamp recordings in rat hypothalamic slice preparations, revealed that cardiovascular related peptides such as atrial natriuretic polypeptides (ANP), B-type polypeptides (BNP), endothelin (ET), angiotensin II (AII) and interleukin-1 beta (IL-1 beta) influence the hypothalamic neurons. ANP modulated the firing rates in the supraoptic nucleus (SON). BNP inhibited the SON neurons and these effects were mediated through cGMP and cGMP-dependent protein kinase. ET also inhibited approximately 60% of SON neurons. By using slice patch-clamp techniques, AII inhibited the transient outward potassium current in the SON neurons. IL-1 beta increased the firing rate and depolarized the membrane of the most SON neurons. A new type of transmitter, nitric oxide (NO), identified as an endothelial-derived relaxing factor (EDRF), modulated the glutaminergic inputs of the SON neurons. The results suggest that cardiovascular related peptides and NO modulate the neuronal activity of neurosecretory cells in the SON.

Sodium nitroprusside modulates NMDA response in the rat supraoptic neurons in vitro.

The modulatory effects of NO on N-methyl-D-aspartate (NMDA)-induced response in neurons of the supraoptic nucleus (SON) were studied by intracellular recording and radioimmunoassay of cyclic nucleotides using the rat brain slice preparation. Depolarization induced by 100 microM NMDA was reduced by application of 1 to 3 mM of the NO-donors, sodium nitroprusside, and isosorbide dinitrate in all 8 neurons and in 6 of 10 neurons, respectively. The scavenger for NO, hemoglobin, and the inhibitor of NO synthase, NG-nitro-L-arginine (LNNA) enhanced the NMDA-induced depolarization in four neurons and two of three neurons, respectively. Intracellular cGMP accumulation induced by NMDA was significantly diminished by LNNA. However, NMDA-induced depolarization was not affected by either the protein kinase inhibitor, N-[2-(methylamino)ethyl]-5- isoquinolinesulfonamide dihydrochloride (H-8), or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). These results indicate that NO reduces NMDA-induced depolarization in a manner that is independent of cGMP and may control the activity of the SON neurons through NMDA receptors.