Inflammation of some visceral sensory systems and autonomic dysfunction in cardiovascular disease.

The sensitization and hypertonicity of visceral afferents are highly relevant to the development and progression of cardiovascular and respiratory disease states. In this review, we described the evidence that the inflammatory process regulates visceral afferent sensitivity and tonicity, affecting the control of the cardiovascular and respiratory system. Some inflammatory mediators like nitric oxide, angiotensin II, endothelin-1, and arginine vasopressin may inhibit baroreceptor afferents and contribute to the baroreflex impairment observed in cardiovascular diseases. Cytokines may act directly on peripheral afferent terminals that transmit information to the central nervous system (CNS). TLR-4 receptors, which recognize lipopolysaccharide, were identified in the nodose and petrosal ganglion and have been implicated in disrupting the blood-brain barrier, which can potentiate the inflammatory process. For example, cytokines may cross the blood-brain barrier to access the CNS. Additionally, pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α and some of their receptors have been identified in the nodose ganglion and carotid body. These pro-inflammatory cytokines also sensitize the dorsal root ganglion or are released in the nucleus of the solitary tract. In cardiovascular disease, pro-inflammatory mediators increase in the brain, heart, vessels, and plasma and may act locally or systemically to activate/sensitize afferent nervous terminals. Recent evidence demonstrated that the carotid body chemoreceptor cells might sense systemic pro-inflammatory molecules, supporting the novel proposal that the carotid body is part of the afferent pathway in the central anti-inflammatory reflexes. The exact mechanisms of how pro-inflammatory mediators affects visceral afferent signals and contribute to the pathophysiology of cardiovascular diseases awaits future research.

Tumores de colon de expansión lateral: características en nuestra población / Laterally spreading tumors: characteristics in our population

Introduction: Colorectal cancer is a rising disease worldwide. In Chile, it is the third leading cause of death associated to gastrointestinal cancer. Optimal preventive management requires surveillance of precursor lesions or early-stage tumors. Laterally spreading tumors (LST) are categorized as nonpolypoid colorectal neoplasms. Since there are no demographic data on these lesions in our country, the aim of our study was to describe the characteristics of LSTs based on our department’s data. Methods: We reviewed the department’s colonoscopy database from 1996 to 2006 to obtain clinical, endoscopic and histological data. We excluded patients with family history of polyposis, prior colorectal cancer and inflammatory bowel disease. Results: Out of 3713 colonoscopies performed, 364 (9.8 percent) adenoma cases were detected; 42 (1.2 percent) of them were catalogued as LSTs. Thirty-three LST patients had complete data and were included in the study. The gender proportion was similar between male and female. Ages ranged from 35 and 92 years (mean +/- SD 66.7 +/- 13.7). The tumor size ranged from 10 to 120 mm (mean +/- SD 28.2 +/- 28.3). According to distribution along the large bowel, 19 (57.5 percent) LSTs were located distally and 14 (42.5 percent) were proximal to the splenic flexure. Histology showed 26 adenomas (14 of them with high-grade dysplasia), 5 adenocarcinomas and 2 hyperplastic lesions. Conclusion: In Chile, LSTs are mainly found in the elderly. It is important to detect these lesions because most of them contain cancer or high-grade dysplasia. Therefore, during colonoscopy, we should focus not only on polypoid lesions, but also on flat lesions.

Introducción: El cáncer colorrectal es una enfermedad emergente a nivel mundial. En nuestro país es la tercera causa de muerte por cáncer del tubo digestivo. Un óptimo manejo preventivo implica la detección y tratamiento de las lesiones precursoras y los cánceres incipientes. Los tumores de expansión lateral (Laterally spreading tumors-LST) se consideran lesiones precursoras no polipoídeas. En Chile no existen datos demográficos de estas lesiones, por lo que el objetivo de este estudio es caracterizar los LST en nuestra población. Métodos: Revisamos la base de datos de las colonoscopias realizadas en nuestro Instituto desde 1996 al 2006, obteniendo datos clínicos y las características endoscópicas e histológicas. Excluimos los pacientes con historia de poliposis familiar, cáncer colorrectal y enfermedad inflamatoria intestinal. Resultados: De 3.713 colonoscopias, se detectaron 364 (9,8 por ciento) casos diagnosticados como adenoma, lesiones planas o LST, de los cuales 42 (1,2 por ciento) se catalogaron como LST. Sólo 33 pacientes con LST tenían disponible el estudio histológico. La proporción por género fue similar entre hombres (17) y mujeres (16). El rango de edad se distribuyó entre 35 y 92 años (promedio +/- DE 66,7 +/- 13,7); el tamaño tumoral fue de 10 a 120 mm (promedio +/- DE 28,2 +/- 28,3). De acuerdo a la distribución en el colon y recto, 19 (57,5 por ciento) LST se localizaron distales al ángulo esplénico y 14 (42,5 por ciento) proximales. El estudio histológico demostró 26 adenomas, 14 de los cuales presentaban displasia de alto grado, 5 adenocarcinomas y 2 lesiones hiperplásicas. Conclusión: En nuestra población los LST se presentan mayoritariamente en la tercera edad. Es importante la detección de estas lesiones, dado que en su mayoría contienen un cáncer o son adenomas con displasia de alto grado. Durante la colonoscopia no solamente debemos enfocarnos en los pólipos sino también en las lesiones planas.

Shunts portosistémicos espontáneos en pacientes con encefalopatía hepática / Spontaneous portal-systemic shunts in hepatic encephalopathy patients: preliminary experience

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by hepatic dysfunction and portosystemic shunting of the intestinal blood. For HE patients nonresponsive to standard therapy, the presence of large spontaneous portal-systemic shunts can occasionally be the cause of the problem. Objective: To assess the prevalence of portal-systemic shunts in patients with cirrhosis and recurrent or persistent HE. Patients and Methods: Ten patients with liver cirrhosis were analyzed who repeatedly developed HE despite pharmacotherapy. Also, we studied seven control patients with cirrhosis and no HE, who were considered the control group. Results: Large spontaneous portal-systemic shunts were detected in all patients with HE and none in the control group (X2 13.1; P: 0.0003). If only splenorenal shunts are considered, the difference is also significant (X2 5.69; p: 0.017). Conclusion: Our study confirmed that the presence of large spontaneous portal-systemic shunts is frequent in patients with cirrhosis and recurrent or persistent HE.

La encefalopatía hepática (EH) es un síndrome neuropsiquiátrico causado por insuficiencia hepática o presencia de shunts portosistémicos (SPS) intra o extrahepáticos. En pacientes con EH refractaria a tratamiento médico habitual se ha planteado que la presencia de SPS podría ser la causa del problema. Objetivo: Evaluar la prevalencia de SPS espontáneos extrahepáticos en pacientes con cirrosis y EH recurrente o persistente. Pacientes y Métodos: Se evaluaron 10 pacientes con EH recurrentes o persistente. También, se estudiaron 7 pacientes con cirrosis y sin EH que se consideraron como grupo control. Resultados: Todos los pacientes con EH recurrente o persistente presentaron SPS; 7 presentaron shunts esplenorrenales espontáneos y 3 presentaron presencia de la vena umbilical recanalizada. Ningún paciente en el grupo control presentó SPS (X2 13,1; p: 0,0003). Si se considera sólo los shunts esplenorrenales, la diferencia también es significativa (X2 5,69; p: 0,017). Conclusión: En nuestros pacientes con cirrosis y EH recurrente o persistente fue frecuente la presencia de SPS espontáneos.

Comparative respiratory strategies of subterranean and fossorial octodontid rodents to cope with hypoxic and hypercapnic atmospheres.

Subterranean rodents construct large and complex burrows and spend most of their lives underground, while fossorial species construct simpler burrows and are more active above ground. An important constraint faced by subterranean mammals is the chronic hypoxia and hypercapnia of the burrow atmosphere. The traits, regarded as "adaptations of rodents to hypoxia and hypercapnia", have been evaluated in only a few subterranean species. In addition, well-studied subterranean taxa are very divergent to their sister groups, making it difficult to assess the adaptive path leading to subterranean life. The closely related sister genera Octodon and Spalacopus of Neotropical rodents offer a unique opportunity to trace the evolution of physiological mechanisms. We studied the ventilatory responses of selected octodontid rodents to selective pressures imposed by the subterranean niche under the working hypothesis that life underground, in hypoxic and hypercapnic conditions, promotes convergent physiological changes. To perform this study we used the following species: Spalacopus cyanus (the subterranean coruros) and Octodon degus (the fossorial degus) from central Chile. Ventilatory tidal volume and respiratory frequency were measured in non-anaesthetized spontaneously breathing animals. Acute hypoxic challenges (O(2) 1-15%) and hypercapnia (CO(2) 10%) were induced to study respiratory strategies using non-invasive whole body pletismography techniques. Our results show that coruros have a larger ventilatory response to acute hypoxia as than degus. On the other hand, hypercapnic respiratory responses in coruros seem to be attenuated when compared to those in degus. Our results suggest that coruros and degus have different respiratory strategies to survive in the hypoxic and hypercapnic atmospheres present in their burrows.

Carotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative link.

Intermittent hypoxia, a feature of obstructive sleep apnoea, potentiates ventilatory hypoxic responses, alters heart rate variability and produces hypertension, partially owing to an enhanced carotid body responsiveness to hypoxia. Since oxidative stress is a potential mediator of both chemosensory and cardiorespiratory alterations, we hypothesised that an antioxidant treatment may prevent these alterations. Accordingly, we studied the effects of ascorbic acid (1.25 g.L(-1) drinking water) on plasma lipid peroxidation, nitrotyrosine and inducible nitric oxide synthase (iNOS) immunoreactivity in the carotid body, ventilatory and carotid chemosensory responses to acute hypoxia, heart rate variability and arterial blood pressure in male Sprague-Dawley rats exposed to 5% O(2); 12 episodes.h(-1); 8 h.day(-1) or sham condition for 21 days. Intermittent hypoxia increased plasma lipid peroxidation, nitrotyrosine and iNOS expression in the carotid body, enhanced carotid chemosensory and ventilatory hypoxic responses, modified heart rate variability and produced hypertension. Ascorbic acid prevented the increased plasma lipid peroxidation and nitrotyrosine formation within the carotid body, and the enhanced carotid chemosensory and ventilatory responses to hypoxia, as well as heart rate variability alterations and hypertension. The present results support an essential role for oxidative stress in the generation of carotid body chemosensory potentiation and systemic cardiorespiratory alterations induced by intermittent hypoxia.

Sustained hypoxia enhances TASK-like current inhibition by acute hypoxia in rat carotid body type-I cells.

Carotid body type-I cells respond to acute hypoxia with membrane depolarization and calcium-dependent neurotransmitter release. The inhibition of a TASK-like background potassium channels plays a key role in initiating this response. Chronic hypoxia enhances the carotid body chemosensory responses evoked by acute hypoxia, however the accurate mechanism by which chronic hypoxia increases carotid body reactivity is not clear. Therefore, we investigated the effects of chronic hypoxia upon TASK-like currents in isolated type-I cells. Carotid bodies were excised from anaesthetized newborn Sprague-Dawley rats and dissociated by collagenase-trypsin digestion. Isolated cells were maintained under 5% CO(2) in normoxic (21% O(2)) or hypoxic (1-2% O(2)) environment for 24 and 48 hours. Channel activity (NPo) was recorded using the cell-attached configuration of the patch-clamp technique. In normoxic and 24 hours hypoxic cultured cells, acute hypoxic stimuli decreases NPo approximately 70% with no effects on current amplitude. On the other hand, in cultured cells subjected to 48 hours of hypoxia, NPo decreases near to 90% in response to acute hypoxia. We concluded that continuous hypoxic exposure enhances the TASK-like channel activity inhibition in response to acute hypoxia. Our results provide a potential mechanism by which chronic hypoxia increases carotid body reactivity.

Neurotransmitters in carotid body function: the case of dopamine--invited article.

The carotid body (CB) is the main peripheral chemoreceptor. The present model of CB chemoreception states that glomus (type I) cells are the primary receptors, which are synaptically connected to the nerve terminals of the petrosal ganglion neurons. In response to hypoxia, hypercapnia and acidosis, glomus cells release one (or more) transmitter(s) which, acting on the nerve terminals of chemosensory neurons, increases the afferent discharge. Among several molecules present in glomus cells, dopamine, acetylcholine and 5'-adenosine-triphosphate have been proposed to be the excitatory transmitters in the CB. Beside these putative excitatory transmitters, other molecules modulate the chemosensory process through direct actions on glomus cells and/or by producing tonic effects on CB blood vessels. In this review, we focus on the role played by dopamine in the CB chemoreception, with emphasis on the open question if the reported differences on its actions on the generation of afferent chemosensory activity reflect true species differences. The available data suggest that dopamine may play a modulatory role within the cat CB, while in the rabbit CB, dopamine is an excitatory transmitter. Therefore, the reported differences on the actions of exogenously applied dopamine and its participation on the generation of afferent chemosensory activity appear to reflect true species differences.

Evidence for histamine as a new modulator of carotid body chemoreception.

It has been proposed that histamine is an excitatory transmitter between the glomus cells of the carotid body (CB) and the nerve endings of the petrosal ganglion (PG) neurons. The histamine biosynthetic pathway and the presence of histamine H1, H2 and H3 receptors have been reported in the CB. Thus, histamine meets some of the criteria to be regarded as a transmitter. However, there is no evidence that glomus cells contain histamine, or whether its application produces chemosensory excitation. Therefore, we studied its immunocytochemical localization on cat CB and its effects on chemosensory activity. Using perfused and superfused in vitro CB and PG preparations, we assessed the effects of histamine hydrochloride on chemosensory discharges and of histamine H1, H2 and H3 receptor blockers. We found the presence of histamine immunoreactivity in dense-core vesicles in glomus cells. In an in vitro CB preparation we performed pharmacological experiments to characterize histamine effects. The application of histamine hydrochloride (0.5-1,000 microg) to the CB produces a dose-dependent increase in the carotid sinus nerve activity. The H1 receptor blockade with pyrilamine 500 nM produces partial decrease of the histamine-induced response, whereas the H2 receptor blockade (ranitidine 100microM) fail to abolish the histamine excitatory effects. Antagonism of the H3 receptor results in an increase in carotid body chemosensory activity. On the other hand, application of histamine to the isolated PG had no effect on the carotid nerve discharge. Our results suggest that histamine is a modulator of the carotid body chemoreception through H1 and H3 receptor activation.

Neuroglobin in aging carotid bodies.

Neuroglobin (Ngb) is a member of the vertebrate globin family expressed particularly in the brain and in the retina. Ngb is concentrated in the mitochondria-containing areas of neurons, and its distribution is correlated with oxygen consumption rates. Previously we have shown that Ngb is expressed in carotid body (CB) tissues. Considering that hypoxia and aging may be linked through a series of adaptive and protective mechanisms (e.g. reduction in mitochondrial numbers), we investigate the role of Ngb during aging and hypoxia. Two groups of six rats (age-matched 3 and 24 months old) were kept in room air as a control groups, the others two groups were kept in a Plexiglas chamber for 12 days in chronic hypoxia (10-12% inspired oxygen). The presence of Ngb in the CB tissue was detected by immunohistochemistry using a polyclonal antibody. Ngb immunoreactivity was significantly higher in CB tissues from young rats exposed to chronic intermittent hypoxia, whereas CB tissues from old rats did not show any significant increase in Ngb levels after hypoxia. Similar to hemoglobin, Ngb may act as a respiratory protein by reversibly binding gaseous ligands NO and O(2) and could act as a NO scavenger and participate in detoxification of Reactive Oxygen Species (ROS) generated under hypoxic conditions.

Cardioventilatory acclimatization induced by chronic intermittent hypoxia.

It has been proposed that chronic intermittent hypoxia (CIH) contributes to generate hypertension in patients with obstructive sleep apnea syndrome and animal models, due to an enhanced sympathetic outflow. A possible contributing mechanism to the CIH-induced hypertension is a potentiation of carotid body (CB) chemosensory responses to hypoxia, but early changes that precede the CIH-induced hypertension are not completely known. Since the variability of heart rate (HRV) has been used as an index of autonomic influences on cardiovascular system, we studied the effects of short and long-term CIH exposure on HRV in animals with or without hypertension. In cats exposed to CIH (PO(2) approximately 75 Torr, 10 times/hr during 8 hr) for 4 days, the ventilatory response to acute hypoxia was potentiated, the arterial pressure remained unchanged, but the HRV power spectrum showed a shift towards the low frequency band. Exposure of rats to CIH (PO(2) approximately 37.5 Torr, 12 times/hr during 8 hr) for 12 days enhanced the ventilatory response to acute hypoxia, but did not increase the arterial pressure. After 21 days of CIH, we found a significant increase of arterial pressure and a shift of the HRV power spectrum towards the low frequency band. Thus, our results support the idea that hypertension induced by long-term CIH was preceded by alterations in the autonomic balance of HRV, associated with an enhance CB chemoreflex sensitivity to hypoxia. Therefore, few days of CIH are enough to enhance the CB reactivity to hypoxia, which contribute to the augmented ventilatory response to hypoxia, and to the early alterations in the autonomic balance of HRV.

Hallazgos endoscópicos en pacientes ambulatorios referidos a endoscopia por síntomas digestivos altos / Endoscopic findings in ambulatory patients referred to endoscopy for upper digestive symptoms

Antecedentes: La realización de endoscopia como primer estudio de un paciente con dispepsia es muy controvertida. Objetivos: Conocer la frecuencia de patología orgánica en pacientes con dispepsia a quienes se les solicita endoscopia digestiva alta, tanto desde la atención primaria como desde los consultorios de especialidades. Métodos: Se analizó la base de datos de endoscopias de nuestro centro en el período 1999-2002. Los diagnósticos de cáncer se confirmaron histológicamente. Resultados: En 10.275 endoscopias practicadas en ese período, 1.488 fueron por dispepsia, 2.536 por síndrome ulceroso y 1.055 por reflujo gastroesofágico. En el grupo con dispepsia se encontró patología orgánica en un 33 por ciento, predominando la gastritis significativa y la esofagitis erosiva. La frecuencia de cáncer gástrico fue baja (0,1 por ciento) y sólo apareció en pacientes sobre 40 años y especialmente en mayores de 60. Lo mismo ocurrió en pacientes referidos por síndrome ulceroso y por reflujo gastroesofágico. Conclusiones: Solicitar endoscopia a pacientes con dispepsia está justificado porque un tercio de ellos tienen patologías de fácil y efectivo tratamiento. El acceso irrestricto a la endoscopia como screening de cáncer gástrico no parece en cambio ser útil en pacientes de menores de 60 años.

Background: The performance of upper digestive endoscopy as a first line study in patients with dyspepsia is highly controversial. Objectives: To investigate the frequency of organic diseases in dyspeptic patients referred from Primary Care centers or from Gastroenterology clinics for upper digestive endoscopy. Methods: The Endoscopy database of our unit was reviewed for the period 1999-2002. The endoscopic diagnosis of gastric cancer was confirmed by positive biopsies. Results: Out of 10.275 endoscopies performed in the study period, the reference diagnosis was: dyspepsia 1.488; ulcer syndrome 2.536 and gastroesophageal reflux 1.055. In the dyspepsia group, 33 percent of cases had some organic pathology, mainly gastritis and erosive esophagitis. The frequency of gastric cancer was low (0.1 percent) and it was found only in patients older than 40 years and specially older than 60 years. Similar results were found in patients referred for ulcer syndrome or gastroesophageal reflux. Conclusions: An upper digestive endoscopy in the initial work up of patients with dyspepsia seems to be acceptable one third of them present organic diseases with easy and effective therapies. On the other hand the irrestrictive acces to endoscopy as screening of gastric cancer does not seem to be useful in patients under 60 years.

Efectos de la infusión aguda de octreotido sobre la función renal en pacientes con cirrosis hepática e hipertensión portal / Effects of acute octreotide infusion on renal function in patients with cirrhosis and portal hypertension

Background: Octreotide is used in the treatment of acute variceal bleeding, based on its inhibitory effects of post-prandial splanchnic hyperemia and splanchnic venoconstriction. The consequences of these haemodynamic changes on renal circulation are not well known in cirrhotic patients. Aim: To evaluate the effects of acute octreotide administration on several parameters of renal function, including free water clearance, in patients with cirrhosis with or without ascites. Patients and Methods: Twenty cirrhotic patients, Child-Pugh A or B, with or without ascites, with esophageal varices, normal renal function and free of medications (vasoactive drugs or diuretics) were assigned to 2 different protocols. Protocol 1: 10 patients were randomized to receive octreotide or placebo, as a bolus followed by a continuous infusion. Glomerular filtration rate (GFR) and renal plasma flow (PRF) were measured, in basal conditions and during the drug or placebo administration. Protocol 2: 10 additional patients were randomized in the same way and free water clearance and urinary sodium excretion were again measured in the basal period and during the drug or placebo infusion. Results: After octreotide or placebo administration no significant changes were observed neither in GFR nor in PRF. The free water clearance decreased significantly during octreotide administration (3.12 ml/min±1.04 SE vs 0.88±0.39, p <.03). In both protocols no changes in mean arterial pressure were observed. Conclusions: Acute administration of octreotide to cirrhotic patients with portal hypertension, with or without ascites, did not produce any change in glomerular filtration rate or in estimated renal plasma blood flow. However the free water clearance decreased significantly. This effect, under chronic administration, could be clinically important and deserves further studies.

Topological shocks in Burgers turbulence.

The dynamics of the multidimensional randomly forced Burgers equation is studied in the limit of vanishing viscosity. It is shown both theoretically and numerically that the shocks have a universal global structure which is determined by the topology of the configuration space. This structure is shown to be particularly rigid for the case of periodic boundary conditions.

Nitric oxide and carotid body chemoreception.

Nitric oxide (NO) has been proposed as an inhibitory modulator of carotid body chemosensory responses to hypoxia. It is believed that NO modulates carotid chemoreception by several mechanisms, which include the control of carotid body vascular tone and oxygen delivery and reduction of the excitability of chemoreceptor cells and petrosal sensory neurons. In addition to the well-known inhibitory effect, we found that NO has a dual (dose-dependent) effect on carotid chemoreception depending on the oxygen pressure level. During hypoxia, NO is primarily an inhibitory modulator of carotid chemoreception, while in normoxia NO increased the chemosensory activity. This excitatory effect produced by NO is likely mediated by an impairment of mitochondrial electron transport and oxidative phosphorylation, which increases the chemosensory activity. The recent findings that mitochondria contain an isoform of NO synthase, which produces significant amounts of NO for regulating their own respiration, suggest that NO may be important for the regulation of mitochondrial energy metabolism and oxygen sensing in the CB.

Detection of respiratory enzyme activity in Giardia cysts and Cryptosporidium oocysts using redox dyes and immunofluorescence techniques.

The fluorescent redox dye 5-cyano-2,3-ditolyl tetrazolium chloride (CTC), combined with fluorescein-labeled antibodies, was tested for the simultaneous detection of the respiratory electron transport system (ETS) activity and enumeration of Giardia cysts and Cryptosporidium oocysts by spectral microfluorometry and epifluorescence microscopy. The reduction of CTC and p-iodonitrotetrazolium violet (INT), a non-fluorescent redox dye, was compared with propidium iodide (PI) and fluorescein diacetate (FDA) for the measurements of Giardia cyst viability over time. According to the PI and FDA staining techniques, nearly 60% of the cysts tested viable at the beginning of the observations; after 21 days their viability decreased to 5%. The redox dyes indicated that approximately 4-10% of the cysts were metabolically active 48 h after they were shed, followed by a decline in enzyme activity to near undetectable levels after 4 days. Spectral analysis on individual cysts indicated that the fluorescence emission of the reduced CTC and the fluorescein-labeled antibodies is distinctive for each compound and suitable for their simultaneous determination by microphotometry, flow cytometry and epifluorescence microscopy. The fluorescence signal remained without alteration when the cysts were transferred onto microscope slides coated with an optical embedding medium and stored at -20 degrees C. The fluorescence intensity of the reduced CTC, when properly standardized, can provide quantitative measurements of ETS activity of the cysts. This is the first report of a method to determine enzyme redox activity on intact cysts applicable to water, laboratory and animal samples.

Dual effects of nitric oxide on cat carotid body chemoreception.

We studied the effects of nitric oxide (NO) released by NO donors on cat carotid body (CB) chemosensory activity during normoxia and hypoxia. CBs excised from pentobarbital sodium-anaesthetized cats were perfused with Tyrode at 38 degrees C and pH 7.40. The frequency of chemosensory discharges (f(x)) was recorded from the carotid sinus nerve, and changes of NO concentration were measured by a chronoamperometric technique, with NO-selective carbon-fiber microelectrodes inserted in the CB. During steady chemosensory excitation induced by hypoxia, bolus injections of NO (DeltaNO = 0. 5-12 microM), released by S-nitroso-N-acetylpenicillamine (SNAP) and 6-(2-hydroxy-1-methyl-nitrosohydrazino)-N-methyl-1-hexanamine++ + (NOC-9), transiently reduced f(x) in a dose-dependent manner. However, during normoxia, the same concentration of NO (DeltaNO = 0. 5-13 microM) released by the NO donors increased f(x) in a dose-dependent manner. The present results show a dual effect of NO on CB chemoreception that is dependent on the PO(2) levels. During hypoxia, NO is predominantly an inhibitor of chemoreception, whereas, in normoxia, NO increased f(x). The mechanisms by which NO produces chemosensory excitation during normoxia remain to be determined.