RESUMEN
Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.
Asunto(s)
Úlcera por Presión , Humanos , Porcinos , Animales , Úlcera por Presión/diagnóstico , Úlcera por Presión/prevención & control , Epidermis , Piel , Edema/diagnóstico , SupuraciónAsunto(s)
Humanos , Masculino , Dermatosis de la Mano/diagnóstico , Coloides , Dermoscopía , BiopsiaAsunto(s)
Humanos , Masculino , Dermatosis de la Mano/diagnóstico , Coloides , Dermoscopía , BiopsiaRESUMEN
Therapeutics promoting myelin synthesis may enhance recovery in demyelinating diseases, such as multiple sclerosis. However, no suitable method exists to quantify myelination. The turnover of galactosylceramide (myelin component) is indicative of myelination in mice, but its turnover has not been determined in humans. Here, six healthy subjects consumed 120 mL 70% D2 O daily for 70 days to label galactosylceramide. We then used mass spectrometry and compartmental modeling to quantify the turnover rate of galactosylceramide in cerebrospinal fluid. Maximum deuterium enrichment of body water ranged from 1.5-3.9%, whereas that of galactosylceramide was much lower: 0.05-0.14%. This suggests a slow turnover rate, which was confirmed by the model-estimated galactosylceramide turnover rate of 0.00168 day-1 , which corresponds to a half-life of 413 days. Additional studies in patients with multiple sclerosis are needed to investigate whether galactosylceramide turnover could be used as an outcome measure in clinical trials with remyelination therapies.
Asunto(s)
Ceramidas/líquido cefalorraquídeo , Deuterio/metabolismo , Voluntarios Sanos , Marcaje Isotópico , Monosacáridos/líquido cefalorraquídeo , Adulto , Anciano , Agua Corporal , Femenino , Humanos , Cinética , Masculino , Persona de Mediana Edad , Modelos Biológicos , Adulto JovenRESUMEN
Fertilization is a key reproductive event in which sperm and egg fuse to generate a new individual. Proper regulation of certain parameters (such as intracellular pH) is crucial for this process. Carbonic anhydrases (CAs) are among the molecular entities that control intracellular pH dynamics in most cells. Unfortunately, little is known about the function of CAs in mammalian sperm physiology. For this reason, we re-explored the expression of CAI, II, IV and XIII in human and mouse sperm. We also measured the level of CA activity, determined by mass spectrometry, and found that it is similar in non-capacitated and capacitated mouse sperm. Importantly, we found that CAII activity accounts for half of the total CA activity in capacitated mouse sperm. Using the general CA inhibitor ethoxyzolamide, we studied how CAs participate in fundamental sperm physiological processes such as motility and acrosome reaction in both species. We found that capacitated human sperm depend strongly on CA activity to support normal motility, while capacitated mouse sperm do not. Finally, we found that CA inhibition increases the acrosome reaction in capacitated human sperm, but not in capacitated mouse sperm.
Asunto(s)
Acrosoma/enzimología , Anhidrasas Carbónicas/metabolismo , Motilidad Espermática/fisiología , Espermatozoides/fisiología , Animales , Células Cultivadas , Activación Enzimática , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Especificidad de la EspecieRESUMEN
Celecoxib (Cx), an anti-inflammatory drug designed to inhibit COX2, can affect some ion channels. T-type (CaV3) channels have been implicated in sperm physiology. Here we report and characterize the Cx induced inhibition of T-type channels in mouse spermatogenic cells. Unexpectedly, Cx can also induce the acrosome reaction (AR), an intracellular Ca(2+) ([Ca(2+)]i) increase and a sperm depolarization. This [Ca(2+)]i increase possibly results from the ability Cx has to alkalinize intracellular pH (pHi), which is known to activate the sperm specific Ca(2+) channel CatSper. As the Cx induced [Ca(2+)]i increase is sensitive to mibefradil, a CatSper blocker, this channel may mediate the Cx-induced Ca(2+) entry leading to the AR. Our observations demonstrate that Cx can compromise fertilization.
Asunto(s)
Reacción Acrosómica/efectos de los fármacos , Antiinflamatorios/farmacología , Canales de Calcio Tipo T/efectos de los fármacos , Pirazoles/farmacología , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Sulfonamidas/farmacología , Animales , Celecoxib , Masculino , RatonesRESUMEN
The neuroprotective effects of oestrogens have been demonstrated against a variety of insults, including excitotoxicity, oxidative stress and cerebral ischemia under certain conditions. However, the molecular mechanisms underlying oestrogen neuroprotection are still unclear. We aimed to determine whether 17beta-oestradiol (E(2)) administration post-hypoxia (p-hx) was neuroprotective and whether these actions were mediated through oestrogen receptors (ER). For this purpose, 12-embyonic day-old chickens were subjected to acute hypoxia [8% (O(2)), 60 min], followed by different reoxygenation periods. To test the neuroprotective effect of E(2) and its mechanism, embryos were injected 30 min after the end of hypoxia with E(2) alone or with ICI 182 780, a competitive antagonist of ER. Cytochrome c (cyt c) release, an indicator of mitochondrial apoptotic pathway, was measured by western blot in optic lobe cytosolic extracts. DNA fragmentation by TUNEL fluorescence and caspase-3 fragmentation by immunofluorescence were detected on optic lobe sections. Acute hypoxia produces a significant increase in cyt c release from mitochondria at 4 h p-hx, followed by an increase in TUNEL positive cells 2 h later (6 h p-hx). Administration of E(2) (0.5 mg/egg) produced a significant decrease in cytosolic cyt c levels at 4 h p-hx, in caspase-3 activation and in TUNEL positive cells at 6 h p-hx compared to vehicle treated embryos. In the E(2)-ICI 182 780 treated embryos, cyt c release, caspase-3 fragmentation and TUNEL positive cells were similar to the hypoxic embryos, thus suggesting the requirement of an E(2)-ER interaction for E(2) mediated neuroprotective effects. In conclusion, E(2) prevents hypoxia-induced cyt c release and posterior cell death and these effects are mediated by oestrogen receptors.
Asunto(s)
Apoptosis , Hipoxia de la Célula/fisiología , Sistema Nervioso Central/crecimiento & desarrollo , Sistema Nervioso Central/metabolismo , Estradiol/farmacología , Receptores de Estrógenos/fisiología , Animales , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Embrión de Pollo , Citocromos c/metabolismo , Fragmentación del ADN/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Fármacos Neuroprotectores/farmacología , Transporte de Proteínas/efectos de los fármacos , Receptores de Estrógenos/metabolismoRESUMEN
The chick optic tectum displays an alternating pattern of cellular and plexiform layers and at embryonic day (ED) 12 there are mainly four cellular layers: transient cell compartment 3 (TCC3), compartment "h-i-j"(C"h-i-j"), stratum griseum centrale (SGC) and subventricular zone (SvZ). In the present work we characterized the programmed cell death (PCD) of these layers and their vulnerability to acute hypoxia at ED12, and also identified the main cellular type involved in hypoxic cell death. The colocalization of three independent markers of cell degeneration: pyknotic nuclei by Hoechst staining, fragmented DNA by TdT-mediated dUTP nick-end labeling (TUNEL), and presence of active caspase-3 by immunofluorescence, was analyzed in embryos that developed in normoxic conditions (control embryos) and embryos that were subjected to hypoxia (8% O(2)/92% N(2)) for 60 min (hypoxic embryos), followed by 0-12 h of normoxic recovery. In control embryos cell death rate within each layer was constant through time, but there were significant differences (P<0.01) in cell death rates among the different layers. In contrast, in hypoxic embryos, a significant increase (P<0.01) in cell death rate was observed in layers TCC3, C"h-i-j" and SGC. This change was evident only at 6 h post-hypoxia, and at later time points cell death rate was similar to control values. Each of these layers had a different vulnerability to the hypoxic event while the SvZ layer was not affected. In addition, the significant colocalization between the neuron specific nuclear protein (NeuN) and TUNEL signal showed that hypoxia affected primarily neurons. In conclusion, our findings demonstrate that in the chick optic tectum at ED12, PCD is layer dependent and that acute hypoxia causes a transient increase in neuronal death in a delayed fashion, which is also layer dependent. The morphological features of the neuronal death process at the light microscope level resembled apoptosis.
Asunto(s)
Diferenciación Celular/fisiología , Hipoxia/patología , Hipoxia/fisiopatología , Colículos Superiores/embriología , Colículos Superiores/patología , Análisis de Varianza , Animales , Caspasa 3/metabolismo , Recuento de Células/métodos , Muerte Celular/fisiología , Embrión de Pollo , Fragmentación del ADN , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica/métodos , Etiquetado Corte-Fin in Situ/métodos , Fosfopiruvato Hidratasa/metabolismo , Factores de TiempoAsunto(s)
Trasplante de Hígado/estadística & datos numéricos , Adolescente , Adulto , Cadáver , Femenino , Humanos , Pruebas de Función Hepática , Trasplante de Hígado/métodos , Trasplante de Hígado/fisiología , Masculino , México , Persona de Mediana Edad , Estudios Retrospectivos , Donantes de TejidosRESUMEN
In six decerebrated and in eight alpha-chloralose anesthetized, paralyzed and mechanically ventilated beagle dogs, we have studied involvement of glutamate and glutamate receptors in transmission of excitatory inputs from the airway sensory receptors to the nucleus tractus solitarius and from this site to airway-related vagal preganglionic cells that regulate the tracheal circulation and the submucosal gland secretion. Stimulation of airway sensory fibers by lung deflation-induced reflex increase in tracheal blood flow and submucosal gland secretion. These responses were diminished by prior administration of AMPA/kainate receptor antagonist CNQX into the fourth ventricle (n=6). Furthermore, topical application or microinjection of AMPA/kainate receptor blockers, into the region of the ventrolateral medulla, where airway-related vagal preganglionic neurons are located, abolished the reflex changes in tracheal submucosal gland secretion (n=8); in these dogs mucosal blood flow was not measured). These findings indicate that reflex increase in tracheal blood flow and submucosal gland secretions are mediated mainly via release of glutamate and activation of the AMPA/kainate subtype of glutamate receptors.
Asunto(s)
Ácido Glutámico/fisiología , Reflejo/fisiología , Mucosa Respiratoria/metabolismo , Tráquea/irrigación sanguínea , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Perros , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Receptores AMPA/antagonistas & inhibidores , Receptores de Ácido Kaínico/antagonistas & inhibidores , Flujo Sanguíneo Regional/fisiología , Respiración , Mucosa Respiratoria/efectos de los fármacosRESUMEN
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates adaptive responses to the lack of oxygen in mammalian cells. HIF-1 consists of two proteins, HIF-1alpha and HIF-1beta. HIF-1alpha accumulates under hypoxic conditions, whereas HIF-1beta is constitutively expressed. HIF-1alpha and HIF-1beta expression were measured during adaptation to hypobaric hypoxia (0.5 atm) in rat cerebral cortex. Western blot analyses indicated that HIF-1alpha rapidly accumulated during the onset of hypoxia and did not fall for 14 days but fell to normal by 21 days despite the continuous low arterial oxygen tension. Immunostaining showed that neurons, astrocytes, ependymal cells, and possibly endothelial cells were the cell types expressing HIF-1alpha. Genes with hypoxia-responsive elements were activated under these conditions, as evidenced by elevated vascular endothelial growth factor and glucose transporter-1 mRNA levels. When 21-day-adapted rats were exposed to a more severe hypoxic challenge (8% oxygen), HIF-1alpha accumulated again. On the basis of these results, we speculate that the vascular remodeling and metabolic changes triggered during prolonged hypoxia are capable of restoring normal tissue oxygen levels.
Asunto(s)
Química Encefálica/fisiología , Proteínas de Unión al ADN/genética , Hipoxia/fisiopatología , Proteínas Nucleares/genética , Factores de Transcripción , Adaptación Fisiológica/fisiología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/metabolismo , Capilares/fisiología , Enfermedad Crónica , Proteínas de Unión al ADN/análisis , Factores de Crecimiento Endotelial/análisis , Factores de Crecimiento Endotelial/genética , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Hipoxia/metabolismo , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Linfocinas/análisis , Linfocinas/genética , Masculino , Neovascularización Fisiológica/fisiología , Proteínas Nucleares/análisis , Oxígeno/farmacología , ARN Mensajero/análisis , Ratas , Ratas Wistar , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that regulates transcriptional activation of several genes responsive to the lack of oxygen, including erythropoietin, vascular endothelial growth factor, glycolytic enzymes, and glucose transporters. Because the involvement of mitochondria in the regulation of HIF-1 has been postulated, we tested the effects of mitochondrial electron transport chain deficiency on HIF-1 protein expression and DNA binding in hypoxic cells. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibits electron transport chain at the level of complex I. MPTP is first converted to a pharmacologically active metabolite 1-methyl-4-phenylpyridinum (MPP+). MPP+ effectively inhibited both complex I activity and hypoxic accumulation of HIF-1alpha protein in dopaminergic cell lines PC12 and CATH.a. In C57BL/6 mice, a single dose of MPTP (15 mg/kg, intraperitoneal) inhibited complex I activity and HIF-1alpha protein accumulation in the striatum in response to a subsequent hypoxic challenge (8% O(2), 4 h). In a genetic model system, 40% complex I-inhibited human-ape xenomitochondrial cybrids, hypoxic induction of HIF-1alpha was severely reduced, and HIF-1 DNA binding was diminished. However, succinate, the mitochondrial complex II substrate, restored the hypoxic response in cybrid cells, suggesting that electron transport chain activity is required for activation of HIF-1. A partial complex I deficiency and a mild reduction in intact cell oxygen consumption effectively prevented hypoxic induction of HIF-1alpha protein.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Mitocondrias/metabolismo , Proteínas Nucleares/metabolismo , Oxígeno/metabolismo , Factores de Transcripción , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , 1-Metil-4-fenilpiridinio/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , ADN/genética , ADN/metabolismo , ADN Mitocondrial/genética , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Transporte de Electrón/efectos de los fármacos , Complejo I de Transporte de Electrón , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Híbridas/efectos de los fármacos , Células Híbridas/metabolismo , Factor 1 Inducible por Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/deficiencia , NADH NADPH Oxidorreductasas/metabolismo , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/metabolismo , Trastornos Parkinsonianos/patología , Primates , Unión Proteica/efectos de los fármacos , Ácido Succínico/farmacología , Células Tumorales CultivadasRESUMEN
This study examined vascular endothelial growth factor (VEGF) expression in rat brain after reversible global cerebral ischemia produced by cardiac arrest and resuscitation. Three alternative splicing forms, VEGF(188), VEGF(164) and VEGF(120), were observed in cortex, hippocampus and brainstem by RT-PCR analysis. After 24 h of recovery from cardiac arrest, mRNA levels corresponding to VEGF(188) and VEGF(164) were significantly increased by about double in all the regions analyzed. These mRNA levels remained elevated at 24 and 48 h of recovery but returned to basal expression after 7 days of recovery. Changes in VEGF(120) expression after cardiac arrest did not reach statistical significance. VEGF protein expression measured by Western blot was also increased by about double at 24 and 48 h of recovery but returned to control levels after 7 days of recovery. VEGF immunohistochemistry localized this increased expression mostly associated with astrocytes. Considering its biological activity, VEGF induction after cardiac arrest and resuscitation may be responsible for the increased vascular permeability and the resultant vasogenic edema, found 24-48 h after reversible global ischemia.
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Isquemia Encefálica/fisiopatología , Encéfalo/metabolismo , Factores de Crecimiento Endotelial/genética , Paro Cardíaco Inducido/efectos adversos , Linfocinas/genética , Resucitación/efectos adversos , Animales , Encéfalo/irrigación sanguínea , Encéfalo/patología , Química Encefálica , Isquemia Encefálica/etiología , Tronco Encefálico/química , Tronco Encefálico/metabolismo , Corteza Cerebral/química , Corteza Cerebral/metabolismo , Factores de Crecimiento Endotelial/biosíntesis , Regulación de la Expresión Génica , Hipocampo/química , Hipocampo/metabolismo , Inmunohistoquímica , Linfocinas/biosíntesis , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The heart rate response to isoproterenol (HR-Iso), density and affinity (kd) of beta-adrenergic (beta-AR) and muscarinic (M2) receptors were compared among three rodents with different generation-life histories of confinement and of high altitude exposure. The European guinea pig (Cavia porcellus) (EGp), a laboratory animal that arrived in Europe after the Spanish Conquest of South America and the Peruvian guinea pig (C. porcellus) (PGp), a semi-wild animal that came from the altiplano to sea level at least 25 generations ago, were used for intra-species comparison. Wistar rats (WR) were used for inter-species comparison as representative of a typical sea level laboratory animal. The HR-Iso was lower in EGp than in the PGp. The PGp showed the highest beta-AR density (P < 0.0005) and the highest beta-AR kd values (P < 0.0005) when compared to both EGp and WR groups (beta-AR Bmax (fmol mg-1 prot), WR, 19 +/- 4; Egp, 34 +/- 10; PGp, 74 +/- 15. beta-AR kd (pM), WR, 24 +/- 10; Egp, 17 +/- 7; PGp, 39 +/- 14). In contrast, PGp showed lower M2 receptor density values than the EGp (P < 0.0005). The WR had the highest M2 receptor densities (M2 Bmax (fmol mg-1 prot), WR, 188 +/- 15; Egp, 147 +/- 9; PGp, 118 +/- 6 and M2 kd (pM), WR, 65 +/- 12; Egp, 67 +/- 6; PGp, 92 +/- 2). The inter and intra-species differences found may be related to their respective history of confinement rather than to their history of exposure to high altitude.
Asunto(s)
Sistema Nervioso Autónomo/fisiología , Corazón/fisiología , Altitud , Animales , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Hipoxia/fisiopatología , Isoproterenol/farmacología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta/metabolismo , Receptores Muscarínicos/metabolismoAsunto(s)
Encéfalo/enzimología , Regulación Enzimológica de la Expresión Génica , Hipoxia/enzimología , Óxido Nítrico Sintasa/genética , Animales , Cerebelo/enzimología , Corteza Cerebral/enzimología , Enfermedad Crónica , Hipocampo/enzimología , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo I , Valores de Referencia , Factores de TiempoAsunto(s)
Diafragma/fisiología , Locus Coeruleus/fisiología , Cianuro de Sodio/farmacología , Animales , Diafragma/efectos de los fármacos , Electromiografía/efectos de los fármacos , Ácido Glutámico/administración & dosificación , Ácido Glutámico/farmacología , Locus Coeruleus/efectos de los fármacos , Masculino , Microinyecciones , Ratas , Ratas Wistar , Respiración/efectos de los fármacos , Insuficiencia Respiratoria , Cianuro de Sodio/administración & dosificación , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
This study examined [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor in membranes prepared from cerebral cortex, hippocampus and corpus striatum of 3 week old rats exposed to 10 weeks of intermittent hypobaric hypoxia (4300 m; 450 Torr) and compared results with those of normoxic controls. The cortex, hippocampus and striatum of hypoxic animals had a 36, 35 and 31% reduction in binding sites (Bmax) and a 29, 32 and 17% decrease (reflecting increased affinity) in the dissociation constant (Kd) when compared to controls. In the cerebral cortex, both glutamate (100 microM) and glycine (10 microM) enhanced 3[H]MK-801 binding by two to 3-fold. Coagonist glutamate, however, had a higher EC50 (0.44 microM) in the hypoxic cortical membranes when compared to controls (0.28 microM). No significant differences were found in the EC50 of glycine. The results show that the NMDA receptor is altered in several brain regions of rats developing in a hypoxic environment.
Asunto(s)
Encéfalo/efectos de los fármacos , Maleato de Dizocilpina/farmacología , Hipoxia/metabolismo , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Animales , Unión Competitiva , Corteza Cerebral/efectos de los fármacos , Hipocampo/efectos de los fármacos , Ratas , Factores de TiempoRESUMEN
We herein describe the regulation of cardiac receptors in a typical high-altitude native animal. Heart rate response to isoproterenol (HRIso) (beats.min-1.mg Iso.kg-1) and atropine, the density of beta-adrenergic (beta AR) and muscarinic (M2) receptors, and the ventricular content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs (Cavia porcellus). Animals native to Lima, Peru (150 m) were studied at sea level (SL) and after 5 wk at 4,300-m altitude (SL-HA). Animals native to Rancas [Pasco, Peru (4,300 m)] were studied at high altitude (HA) and after 5 wk at SL (HA-SL). HA animals had a lower HRIso, maximum number of beta AR binding sites (Bmax), beta AR dissociation constant (Kd), NE, and DA (P < 0.05) and a higher M2 Bmax (P < 0.001) when compared with the SL group. HA-SL showed an increase of the HRIso, beta Ar Kd, and NE (P < 0.05) and a decrease of the M2 Bmax and Kd (P < 0.0001) when compared with the HA group. The present study demonstrates the differential regulation and reversibility of the autonomic control in the guinea pig heart.