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Biomedical subjects

H Moreno

Publications and source records attributed to H Moreno.

At least 19 recordsLinked to original sources
PubMed2005

The role of nitric oxide in the emotional learning of rats in the plus-maze.

The present study evaluated the role of nitric oxide (NO) in the transfer latency (TL) paradigm in the elevated plus-maze. Male Wistar rats received i.p. injections of either 0.9% Saline, N(omega) Nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of NO synthesis), d-NAME (inert isomer), scopolamine (SCO, antagonist of muscarinic receptors), or MK-801 (antagonist of NMDA receptors) and, after 30 min, were submitted to TL procedure. In an independent experiment, the ability of the same L-NAME treatments in changing the arterial pressure and blood glucose level (BGL) was evaluated in conscious rats. The treatment with SCO (1 mg kg(-1)), MK-801 (0.15 mg kg(-1)) and L-NAME (10 and 50 mg kg(-1)), but not with D-NAME, impaired the TL learning. The L-NAME-induced TL deficit was counteracted by L-ARG (100 and 200 mg kg(-1)), while the co-administration of sub-effective doses of L-NAME and MK-801 failed to impair the TL learning. The L-NAME (50 mg kg(-1)) treatment failed to alter the BGL. All treatments with L-NAME induced hypertension, but the rats treated with L-NAME (5 mg kg(-1)) were still able to learn the TL task. The data indicate that the TL deficit induced by L-NAME (10 and 50 mg kg(-1)) is not due to either hypertension or changes in the BGL. It is also possible to establish that NO production is important for emotional learning underlying the TL procedure in rats.

Animals↗
PubMed2004

[Diffuse pulmonary ossification associated with idiopathic pulmonary fibrosis].

Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79-year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient s course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae --some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis.

Aged↗
PubMed2001

A novel functional co-operation between MyoD, MEF2 and TRalpha1 is sufficient for the induction of GLUT4 gene transcription.

We report tripartite co-operation between MyoD, myocyte enhancer factor-2 (MEF2) and the thyroid hormone receptor (TRalpha1) that takes place in the context of an 82-bp muscle-specific enhancer in the rat insulin-responsive glucose transporter (GLUT4) gene that is active in both cardiac and skeletal muscle. In the L6E9 skeletal muscle cell line and in 10T1/2 fibroblasts, a powerful synergistic activation of the GLUT4 enhancer relied on the over-expression of MyoD, MEF2 and TRalpha1 and the integrity of their respective binding sites, and occurred when linked to either a heterologous promoter or in the context of the native GLUT4 promoter. In cardiac myocytes, enhancer activity was dependent on the binding sites for MEF2 and TRalpha1. Furthermore, we show that in 10T1/2 fibroblasts, the forced expression of MyoD, MEF2 and TRalpha1 induced the expression of the endogenous, otherwise silent, GLUT4 gene. In all, our results indicate a novel functional co-operation between these three factors which is required for full activation of GLUT4 transcription.

Animals↗
PubMed2001

Nitric oxide may underlie learned fear in the elevated T-maze.

The present study evaluated the role of nitric oxide (NO) in learned and innate fear in rats submitted to the elevated T-maze (ETM). Learned and innate fear were evaluated through the inhibitory avoidance and escape behaviour from the open arms, respectively. Rats treated with the inhibitor of NO synthesis N(omega)-nitro-L-Arginine methyl ester (L-NAME; 5, 10, and 50 mg. kg(-1)) were able to learn the inhibitory avoidance. However, L-NAME (50 mg. kg(-1)), but not its inert isomer N(omega)-nitro-D-arginine methyl ester (D-NAME, 50 mg. kg(-1)), impaired the inhibitory avoidance 2 with no change in the baseline values, thus suggesting an anxiolytic-like effect without locomotor impairment. All treatments with L-NAME were able to induce increased mean arterial pressure (MAP), measured indirectly through the animal's tail. The treatment with L-NAME (5 and 10 mg. kg(-1)) failed to induce anxiolysis but significantly increased the MAP of the animals, which indicates that hypertension per se, did not underlie anxiolysis induced by L-NAME. L-Arginine, the precursor molecule for NO synthesis, facilitated the inhibitory avoidance and counteracted the L-NAME (50 mg. kg(-1))-induced anxiolysis. Neither previous treatment was able to change the escape behaviour. The results indicate that NO may underlie learned, but not innate, fear in the ETM.

Animals↗
PubMed2001

Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats.

Nicotine may contribute to smoking-induced endothelial dysfunction because of its ability to impair endothelium-dependent vasodilatation. We investigated whether the acute administration of nicotine changes the hypotensive responses to bradykinin in rats. The effects of pre-treatment with losartan or enalapril on the nicotine-induced changes in the responses to bradykinin were also evaluated. In study 1, anesthetized rats were cannulated via carotid artery for the measurement of mean arterial pressure. Dose-response curves to bradykinin (0.1, 0.4, 1.6, 6.4, 25 and 100 microg/kg) were generated before and 10 min after the injection of nicotine (200 microg/kg, i.v.) or saline. The individual dose-response curves were fitted to a four-parameter logistic equation using the ALLFIT program, which provided an estimate of the maximal response (E(max)) and of the dose of bradykinin producing the half-maximal response (ED(50)). In study 2, rats were pre-treated orally with losartan (10 mg/kg/day) or enalapril maleate (25 mg/kg/day) for 2 weeks. Control rats received tap water alone. After pre-treatment, the rats were anesthetized and used as described in study 1. Nicotine decreased the E(max) (from 73.0+/-7.5 to 65.7+/-3.3 mm Hg; P<0.05) but did not affect the ED(50). In study 2, losartan or enalapril did not affect nicotine-induced decrease in responses to bradykinin; E(max) decreased in both groups (from 68.7+/-6.3 to 62.8+/-4.2 mm Hg, and from 53.8+/-13.0 to 43.1+/-7.1 mm Hg, respectively; P<0.05) without significantly changing the ED(50). These results suggest that nicotine impairs the endothelium-dependent hypotensive responses to bradykinin. This effect is not influenced by inhibition of the angiotensin-converting enzyme or by blockade of the angiotensin AT(1) receptors.

Angiotensin Receptor Antagonists↗
PubMed2001

Modulation of Kv3 potassium channels expressed in CHO cells by a nitric oxide-activated phosphatase.

1.Voltage-gated K+ channels containing Kv3 subunits play specific roles in the repolarization of action potentials. Kv3 channels are expressed in selective populations of CNS neurons and are thought to be important in facilitating sustained and/or repetitive high frequency firing. Regulation of the activity of Kv3 channels by neurotransmitters could have profound effects on the repetitive firing characteristics of those neurons. 2.Kv3 channels are found in several neuronal populations in the CNS that express nitric oxide synthases (NOSs). We therefore investigated whether Kv3 channels are modulated by the signalling gas nitric oxide (NO). 3. We found that Kv3.1 and Kv3.2 currents are potentially suppressed by D-NONOate and other NO donors. The effects of NO on these currents are mediated by the activation of guanylyl cyclase (GC), since they are prevented by Methylene Blue, an inhibitor of GC, and by ODQ, a specific inhibitor of the soluble form of GC. Moreover, application of 8-Br-cGMP, a permeant analogue of cGMP, also blocked Kv3.1 and Kv3.2 currents. 4.KT5283, a cGMP-dependent protein kinase (PKG) blocker, prevented the inhibition of Kv3.1 and Kv3.2 currents by D-NONOate and 8-Br-cGMP. This indicates that activation of PKG as a result of the increase in intracellular cGMP levels produced by D-NONOate or 8-Br-cGMP is necessary for channel block. 5. Although the effects of NO on Kv3.1 and Kv3.2 channels require PKG activity, two observations suggest that they are not mediated by phosphorylation of channel proteins: (a) the reagents affect both Kv3.2 and Kv3.1 channels, although only Kv3.2 proteins have a putative PKA-PKG phosphorylation site, and (b) mutation of the PKA-PKG phosphorylation site in Kv3.2 does not interfere with the effects of NO or cGMP. 6. The inhibitory effects of NO and cGMP on Kv3.1 and Kv3.2 currents appear to be mediated by the activation of serine-threonine phosphatase, since they are blocked by low doses of okadaic acid. Furthermore, direct intracellular application of the catalytic subunit of protein phosphatase 2A inhibited Kv3.2 currents, indicating that activity of PKG-induced phosphatase is necessary and sufficient to inhibit these channels. 7. The results suggest that basal phosphorylation of Kv3 channel proteins is required for proper channel function. Activation of phosphatases via NO or other signals that increase cGMP might be a potent mechanism to regulate Kv3 channel activity in neurons.

Alkaloids↗
PubMed2001

Cardiovascular effects of transdermal nicotine in mildly hypertensive smokers.

Smoking potentiates the enhanced cardiovascular risk of hypertensive patients. Although nicotine replacement therapy is safe when used by healthy individuals to quit smoking, there is no evidence that nicotine replacement therapy is safe in hypertensive smokers. In this crossover, single-blinded, placebo-controlled study, we compared for 4 h the acute effects of transdermal nicotine on the mean arterial pressure (MAP) and heart rate (HR) of mildly hypertensive smokers treated with hydrochlorothiazide with the responses in normotensive smokers and nonsmokers monitored with Finapres and ambulatory blood pressure systems. The plasma concentrations of thromboxane B2 (TXB2, the stable breakdown product of TXA2) were also measured by ELISA to assess whether transdermal nicotine acutely affects TXA2 production. The use of 21-mg nicotine patches increased the MAP and HR in nonsmokers (from 94+/-4 mm Hg and 69+/-3 beats/min to 117+/-7 mm Hg and 83+/-3 beats/min, respectively; P < .05) as well as the MAP in normotensive smokers (from 83+/-4 to 106+/-7 mm Hg; P < .05). However, MAP and HR remained unaltered in hypertensive smokers after transdermal nicotine. Higher basal TXB2 levels were observed in hypertensive smokers compared with normotensive smokers and nonsmokers (2019+/-402 v 670+/-167 and 556+/-68 pg/mL, respectively; P < .05). Transdermal nicotine increased the TXB2 levels only in nonsmokers (P < .05). These data indicate that the use of transdermal nicotine in mildly hypertensive smokers is probably safe. Further studies involving other classes of hypertensive patients are warranted.

Administration, Cutaneous↗
PubMed2001

Expression and distribution of NOS1 and NOS3 in the myocardium of angiotensin II-infused rats.

Studies have indicated a complex functional interaction between angiotensin (Ang) II and NO in the heart. The purpose of the present study was to examine the protein expression and tissue distribution of NO synthases 1 (NOS1) and 3 (NOS3) in the myocardium of rats that underwent continuous infusion of Ang II at 2 different rates (10 and 40 ng. kg(-1). min(-1)) for 6 days. Mean arterial pressure increased by approximately 15 mm Hg in rats infused with Ang II at 40 ng. kg(-1). min(-1), but it remained close to the values observed in saline-infused rats ( approximately 110 mm Hg) when Ang II was infused at 10 ng. kg(-1). min(-1). The protein expression of a 160-kDa NOS1 and a 135-kDa NOS3 were found to increase ( approximately 200%) in the myocardium of rats infused with both subpressor and pressor doses of Ang II. Immunohistochemistry studies showed that NOS1 and NOS3 are differentially expressed in myocardial cells. NOS1 was detected in cardiac myocytes and in smooth muscle cells of small and large coronary arteries, whereas NOS3 was detected in the endothelium and in perivascular and interstitial tissues, but NOS3 was not detected in cardiac or smooth muscle cells. Ang II infusion enhanced the tissue immunoreactivity of both isoforms in their specific locations but did not change the distribution throughout the myocardium. Myocardium staining with anti-angiotensin type 1 (AT(1)) receptor antibody indicated that AT(1) receptor is expressed in cardiac myocytes, coronary smooth muscle cells, and interstitial and perivascular tissues. Ang II infusion did not change the protein expression and distribution of AT(1) receptor in the myocardium. These results indicate that long-term increases in the circulating levels of Ang II modulate the protein expression of NOS1 and NOS3 and, consequently, the function of the local myocardial NO system.

Angiotensin II↗
PubMed2001

Prevalence of metronidazole-resistant Trichomonas vaginalis in a gynecology clinic.

OBJECTIVE: To determine the prevalence of in vitro resistance to metronidazole among unselected isolates of Trichomonas vaginalis and correlate in vitro findings with response to metronidazole therapy. STUDY DESIGN: Vaginal fluid from women attending a gynecology clinic at an urban hospital was cultured, isolates were tested for in vitro resistance to metronidazole, and these results were correlated with therapeutic outcome. RESULTS: Among 911 women, T vaginalis was detected by culture in 82 (9.0%). Of the 82 isolates, 2 (2.4%; 95% CI, 0.3-8.5%) had low-level in vitro resistance (minimum lethal concentration, 50 micrograms/mL). Women with positive wet mount examinations were treated with metronidazole, 2 g, once and asked to return in one week. Of the 42 infected women agreeing to return for a repeat examination and culture, 26 (61.9%) did, and all (including one woman with a resistant isolate) were cured. CONCLUSION: Isolates of T vaginalis resistant to metronidazole occur widely throughout the United States. Although the in vitro susceptibility of T vaginalis to metronidazole has been very poorly studied, our study is consistent with a decade-old prevalence estimate of in vitro resistance (5%), and suggests that high-level resistance is uncommon. This study confirmed, in the absence of reinfection, the continuing clinical effectiveness of single-dose metronidazole for the large majority of trichomoniasis cases.

Adult↗
PubMed2000

Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity.

GABAergic (GABA = gamma-aminobutyric acid) neurons from different brain regions contain high levels of parvalbumin, both in their soma and in their neurites. Parvalbumin is a slow Ca(2+) buffer that may affect the amplitude and time course of intracellular Ca(2+) transients in terminals after an action potential, and hence may regulate short-term synaptic plasticity. To test this possibility, we have applied paired-pulse stimulations (with 30- to 300-ms intervals) at GABAergic synapses between interneurons and Purkinje cells, both in wild-type (PV+/+) mice and in parvalbumin knockout (PV-/-) mice. We observed paired-pulse depression in PV+/+ mice, but paired-pulse facilitation in PV-/- mice. In paired recordings of connected interneuron-Purkinje cells, dialysis of the presynaptic interneuron with the slow Ca(2+) buffer EGTA (1 mM) rescues paired-pulse depression in PV-/- mice. These data show that parvalbumin potently modulates short-term synaptic plasticity.

2-Amino-5-phosphonovalerate↗
PubMed2000

Endothelin-1 attenuates bradykinin-induced hypotension in rats.

Endothelin-1 has vasoconstrictor and mitogenic properties and may contribute to the pathogenesis of hypertension by enhancing vasoconstrictor mechanisms. In this study, we investigated the ability of endothelin-1 decrease the hypotensive effects of the vasodilator bradykinin in anesthetized rats. We also studied the effects a two-week oral pre-treatment with losartan (10 mg/kg/day) or enalapril (25 mg/kg/day) on endothelin-1-induced changes in the hypotensive responses to bradykinin. Bradykinin (0.4, 1.6, 6.4, and 25 mcg/kg, i.v.) induced dose-dependent hypotensive responses which were attenuated (P<0.05) by endothelin-1 (2 mcg/kg, i.v.). This effect of endothelin-1 was abolished by the mixed endothelin receptor antagonist N-Acetyl-alpha-[10,11-Dihydro-5H-dibenzo[a, d]cycloheptadien-5-yl]-D-Gly-Leu-Asp-Ile-Ile-Trp (PD145065, 1 mg/kg, i.v.). Endothelin-1 also decreased (P<0.05) the responses to bradykinin in rats pre-treated with losartan, but had no effect in rats pre-treated with enalapril. These results suggest that endothelin-1 may contribute to the development of hypertension by decreasing the responses to bradykinin through a mechanism not involving angiotensin AT(1) receptors, although the inhibition of angiotensin converting enzyme blunted the effect of endothelin-1.

Administration, Oral↗
PubMed2000

Endothelin ET(A) receptor antagonism attenuates the pressor effects of nicotine in rats.

The increased endothelin-1 levels observed after smoking may result from nicotine-stimulated endothelin-1 production by endothelial cells. In this study, we investigated the effects of selective endothelin ET(A) receptors antagonist Cycle D-a-aspartyl-L-prolyl-D-isoleucyl-D-tryptophyl (JKC 301) and of endothelin ET(B) receptors antagonist N-cis-2, 6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-m ethoxycarbonyl-tryptophanyl-norleucine (BQ 788) on the changes in mean arterial pressure, heart rate, and plasma thromboxane B(2) (the stable product of thromboxane A(2)) levels caused by increasing doses of nicotine (0.6, 2, 6, and 20 micromol/kg) in anesthetised rats. Nicotine (0.6, 2, and 6 micromol/kg) significantly increased the mean arterial pressure in control and BQ 788-pretreated rats, while only a nicotine dose of 2 micromol/kg) increased the mean arterial pressure in JKC 301-pretreated animals. There were no differences in the nicotine-induced changes in heart rate or in the increases in thromboxane B(2) levels among the groups treated with saline, JKC 301 and BQ 788. These results demonstrate that whereas the antagonism of endothelin ET(A) receptors attenuated the increase in blood pressure after nicotine injections, endothelin ET(B) receptor antagonism had no such effect. In addition, the antagonism of endothelin ET(A) or ET(B) receptors did not affect thromboxane A(2) production after nicotine administration. These findings suggest that endothelin-1 may have a role in the acute effects of nicotine.

Animals↗
PubMed2000

Plasma cGMP levels in air embolism-induced acute lung injury.

PURPOSE: An impaired generation of cGMP may account for the pulmonary hypertension seen in acute lung injury (ALI). We investigated the hemodynamic changes and the plasma levels of cGMP during air embolism-induced ALI in two different models: venous air infusion (VAI) and massive air embolism (MAE). MATERIALS AND METHODS: After a baseline hemodynamic evaluation, anesthetized dogs received a VAI (0.2 mL/kg/min, n = 10) or a bolus of air (MAE, 2.5 mL/kg, n = 10) intravenously. A group of control dogs (n = 5) received no further treatment. Hemodynamic evaluation was performed 5 to 60 minutes after the VAI was initiated or after the MAE. Blood samples were drawn for plasma cGMP determinations. RESULTS: The VAI increased the pulmonary artery pressure (by 181%, P<.05) after 15 minutes of air infusion without changing the cardiac index. The MAE increased the pulmonary artery pressure (by 252%) and decreased the cardiac index (by 31%) 5 minutes after the air injection (both P<.05). These variables returned to baseline 15 to 30 minutes thereafter. The cGMP concentrations remained unaltered during the VAI. In contrast, cGMP levels increased 26% (P<.05) by 15 minutes after the MAE and returned to basal levels thereafter. CONCLUSION: These findings suggest that a lack of increase in the production of the cGMP may account for the pulmonary hypertension seen in air embolism-induced ALI. Additionally, the small increase in cGMP levels after the MAE may reflect the more severe hemodynamic derangement in this setting.

Analysis of Variance↗
PubMed2000

Nicotine impairs endothelium-dependent dilatation in human veins in vivo.

BACKGROUND: Cigarette smoking is associated with impaired endothelium-dependent dilatation in human veins and arteries. An in vivo study in animals suggests that nicotine may contribute to this abnormality. We tested the hypothesis that local administration of nicotine at a dose reproducing the plasma concentration observed during smoking would impair endothelium-dependent vasodilatation in human veins in vivo. METHODS: We studied 11 healthy nonsmokers with the dorsal hand vein compliance technique. After 70% to 80% preconstriction with phenylephrine, endothelium-dependent venous relaxation was assessed by infusion of bradykinin (1 to 278 ng/min), a potent vasodilator acting primarily in this model through endothelial release of nitric oxide and prostanoids. Sodium nitroprusside (0.0001 to 3166 ng/min) was used to test endothelium-independent relaxation. Dose-response curves were constructed before and during nicotine coinfusion at a rate of 40 ng/min, reproducing a plasma concentration of 15 ng/mL. RESULTS: After a 10-minute preinfusion, nicotine administration was associated with a loss in sensitivity to bradykinin (P < .001). After 30 and 60 minutes of preinfusion with nicotine, the venorelaxant effect of bradykinin was further reduced (P < .001). A similar inhibition of the response to bradykinin by nicotine persisted in the presence of indomethacin (INN, indomethacin). Coinfusion of nicotine did not attenuate sodium nitroprusside-induced venodiiation. CONCLUSION: The results show that acute local exposure to nicotine in vivo is associated with an impaired response to endothelium-derived nitric oxide in human veins. This finding may provide further insight into the pathophysiology of smoking-induced endothelial dysfunction.

Adult↗
PubMed2000

Transdermal nicotine mimics the smoking-induced endothelial dysfunction.

BACKGROUND: Cigarette smoking is a major risk factor for coronary artery disease and causes endothelial dysfunction, perhaps by decreasing the availability of nitric oxide availability in arteries and veins. Nicotine in cigarette smoke may be responsible for this impaired endothelial response. METHODS: We studied nine healthy nonsmokers and 12 healthy mild to moderate smokers by use of the dorsal hand vein compliance technique. Dose-response curves to bradykinin and sodium nitroprusside were obtained to test the endothelium-dependent and endothelium-independent vasorelaxation before and during the use of a nicotine (21 mg) patch. Mean arterial blood pressure and heart rate were measured beat-to-beat during the 4-hour study and serial blood samples were drawn to assay plasma thromboxane B2 levels. RESULTS: Transdermal nicotine reduced the venous responsiveness to bradykinin in nonsmokers (Emax = 88.0% +/- 17.9% and 54.3% +/- 14.9%, respectively, before and after the nicotine patch; P < .05); the latter response was similar to that in smokers (Emax = 56.3% +/- 16.6%). Sodium nitroprusside-induced venodilation was unaltered. Mean arterial blood pressure increased in both smokers and nonsmokers. Transdermal nicotine increased the plasma thromboxane B2 concentrations only among nonsmokers. CONCLUSION: These findings indicate that nicotine can have a major role in the impaired endothelial function in smokers. The results probably also reflect what occurs in arterial beds because the nicotine patches increased the mean arterial blood pressure in both smokers and nonsmokers.

Administration, Cutaneous↗