RESUMO
The distal colon epithelium of rats submitted to chronic hypoxia shows higher short-circuit current (Isc) which, unlike non-hypoxic rat epithelium, has an amiloride-sensitive component despite low serum aldosterone levels. Isc and oxygen consumption (QO2) were simultaneously measured in mucosae from rats submitted to 0.5 atm for 10 days and from control rats in a modified Ussing chamber. Hypoxia increased Isc but not QO2. The slope of the regression line between Isc and QO2 reduction after ouabain addition was decreased in epithelia from hypoxic rats (P = 0.03). Chloride secretion blockade reduced Isc and QO2 in both groups, while sodium channel blockade did so only in the hypoxic group. Dual blockade in hypoxic rat epithelia caused correlated (P = 0.0025) additive decreases in Isc and QO2. Presented results suggest that chronic hypoxia induces an improved coupling between QO2 and electrogenic ion transport, and electrogenic sodium absorption despite low aldosterone levels.
Assuntos
Colo/metabolismo , Hipóxia/fisiopatologia , Transporte de Íons/fisiologia , Consumo de Oxigênio/fisiologia , Sódio/metabolismo , Aldosterona/sangue , Análise de Variância , Animais , Pressão Atmosférica , Doença Crônica , Eletrofisiologia , Masculino , Ratos , Ratos WistarRESUMO
Electrophysiological events occur early after fertilization, along with changes in intracellular Ca2+ concentration. Passive electrical parameters were determined in golden hamster oocytes by whole cell patch-clamp method. In separate experiments the effect of 4-aminopyridine on resting oocytes was tested. The single-channel patch clamp configuration was employed to assess the electrical response to fertilization with homologous sperm. Structure of oocytes submitted to patch clamp was evaluated with scanning electron microscopy and found to be preserved. Oocyte diameter was 70.2 +/- 2.2 microm; their resting parameters were: membrane potential 23.8 +/- 0.8 mV; total membrane specific resistance 519.1 +/- 94.6 ohms.cm2, and specific capacity 0.99 +/- 0.03 microF.cm(-2). Total membrane current was decreased by 42 % by 4-aminopyridine. Control oocytes and oocytes exposed to sperm differed in their membrane currents in response to a voltage ramp clamping membrane potential from - 100 mV to + 100 mV. In both cases, currents were largest at the most negative potentials, but sperm-exposed oocytes had larger currents. Additionally, while in control oocytes the current was inward at negative potentials but outward at positive potentials, in the presence of spermatozoa oocytes was inward within the whole voltage range tested. This latter current may represent Ca2+ entry.
Assuntos
Interações Espermatozoide-Óvulo/fisiologia , 4-Aminopiridina/farmacologia , Animais , Cricetinae , Eletrofisiologia , Feminino , Técnicas In Vitro , Masculino , Potenciais da Membrana , Mesocricetus , Microscopia Eletrônica de Varredura , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Oócitos/ultraestrutura , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia , Interações Espermatozoide-Óvulo/efeitos dos fármacosRESUMO
Electrophysiological events occur early after fertilization, along with changes in intracellular Ca2+ concentration. Passive electrical parameters were determined in golden hamster oocytes by whole cell patch-clamp method. In separate experiments the effect of 4-aminopyridine on resting oocytes was tested. The single-channel patch clamp configuration was employed to assess the electrical response to fertilization with homologous sperm. Structure of oocytes submitted to patch clamp was evaluated with scanning electron microscopy and found to be preserved.Oocyte diameter was 70.2 ± 2.2 Am; their resting parameters were: membrane potential 23.8 ± 0.8 mV; total membrane specific resistance 519.1 ± 94.6 Ù.cm2, and specific capacity 0.99 ± 0.03 AF.cm-2. Total membrane current was decreased by 42 % by 4-aminopyridine.Control oocytes and oocytes exposed to sperm differed in their membrane currents in response to a voltage ramp clamping membrane potential from - 100 mV to + 100 mV. In both cases, currents were largest at the most negative potentials, but sperm-exposed oocytes had larger currents. Additionally, while in controloocytes the current was inward at negative potentials but outward at positive potentials, in the presence of spermatozoa oocytes was inward within the whole voltage range tested. This latter current may represent Ca2+ en try(AU)
Assuntos
Masculino , Cobaias , Animais , Feminino , Oócitos/ultraestrutura , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Técnicas de Patch-Clamp/veterinária , Bloqueadores dos Canais de Potássio/farmacologia , Fertilização/fisiologia , MesocricetusRESUMO
Electrophysiological events occur early after fertilization, along with changes in intracellular Ca2+ concentration. Passive electrical parameters were determined in golden hamster oocytes by whole cell patch-clamp method. In separate experiments the effect of 4-aminopyridine on resting oocytes was tested. The single-channel patch clamp configuration was employed to assess the electrical response to fertilization with homologous sperm. Structure of oocytes submitted to patch clamp was evaluated with scanning electron microscopy and found to be preserved.Oocyte diameter was 70.2 ± 2.2 Am; their resting parameters were: membrane potential 23.8 ± 0.8 mV; total membrane specific resistance 519.1 ± 94.6 Ù.cm2, and specific capacity 0.99 ± 0.03 AF.cm-2. Total membrane current was decreased by 42 % by 4-aminopyridine.Control oocytes and oocytes exposed to sperm differed in their membrane currents in response to a voltage ramp clamping membrane potential from - 100 mV to + 100 mV. In both cases, currents were largest at the most negative potentials, but sperm-exposed oocytes had larger currents. Additionally, while in controloocytes the current was inward at negative potentials but outward at positive potentials, in the presence of spermatozoa oocytes was inward within the whole voltage range tested. This latter current may represent Ca2+ en try(AU)
Assuntos
Masculino , Cobaias , Animais , Feminino , Oócitos/ultraestrutura , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Técnicas de Patch-Clamp/veterinária , Bloqueadores dos Canais de Potássio/farmacologia , Fertilização/fisiologia , MesocricetusRESUMO
Electrophysiological events occur early after fertilization, along with changes in intracellular Ca2+ concentration. Passive electrical parameters were determined in golden hamster oocytes by whole cell patch-clamp method. In separate experiments the effect of 4-aminopyridine on resting oocytes was tested. The single-channel patch clamp configuration was employed to assess the electrical response to fertilization with homologous sperm. Structure of oocytes submitted to patch clamp was evaluated with scanning electron microscopy and found to be preserved.Oocyte diameter was 70.2 ± 2.2 µm; their resting parameters were: membrane potential 23.8 ± 0.8 mV; total membrane specific resistance 519.1 ± 94.6 Ù.cm2, and specific capacity 0.99 ± 0.03 µF.cm-2. Total membrane current was decreased by 42 % by 4-aminopyridine.Control oocytes and oocytes exposed to sperm differed in their membrane currents in response to a voltage ramp clamping membrane potential from - 100 mV to + 100 mV. In both cases, currents were largest at the most negative potentials, but sperm-exposed oocytes had larger currents. Additionally, while in controloocytes the current was inward at negative potentials but outward at positive potentials, in the presence of spermatozoa oocytes was inward within the whole voltage range tested. This latter current may represent Ca2+ en try
Assuntos
Masculino , Cobaias , Animais , Feminino , Bloqueadores dos Canais de Potássio/farmacologia , Fertilização/fisiologia , Mesocricetus , Oócitos , Oócitos/fisiologia , Oócitos/ultraestrutura , Técnicas de Patch-Clamp/veterináriaRESUMO
Chronic hypobaric hypoxia is a physiological environmental stressor. While its effects on most major organ systems have been extensively studied, few works have addressed hypoxia-induced changes in intestinal transport. The effects of cyclooxygenase blockade with indomethacin on short-circuit current (Isc) and oxygen consumption (QO2) of the distal colonic epithelium of control rats and rats submitted to hypoxia for 10 days at 0.52 atm were studied. Isolated mucosae were mounted in an Ussing chamber modified for measuring QO2 while preserving transepithelial vectorial transport. Amiloride was added to the mucosal hemichamber to block a sodium component of Isc present in hypoxic rats. In this condition, basal Isc did not differ between the hypoxic and the control group, but QO2 was higher in the former. Indomethacin (30 micromol/L) reduced Isc to the same extent in both groups, but QO2 reduction was larger in the hypoxic group. Pharmacological blockade of chloride secretion and a low-chloride solution abolished the indomethacin-induced reductions of Isc in both groups, and the reduction of QO2 in controls, and attenuated but did not suppress the QO2 reduction in the hypoxic group. Linear regression analysis of QO2 changes versus Isc changes yielded a significant correlation for both groups, with regression lines with the same slope, but a higher position in bypoxic animals. Results suggest that spontaneously releasedprostaglandins are equally important for maintaining colonic chloride secretion in hypoxic as in normoxic rats, but that, in the former, indomethacin has an additional effect on QO2 which is unrelated to ion transport.
Assuntos
Colo/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Hipóxia/metabolismo , Indometacina/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Animais , Colo/metabolismo , Inibidores de Ciclo-Oxigenase/metabolismo , Modelos Animais de Doenças , Indometacina/metabolismo , Masculino , Consumo de Oxigênio/fisiologia , Ratos , Ratos WistarRESUMO
Chronic hypobaric hypoxia is a physiological environmental stressor. While its effects on most major organsystems have been extensively studied, few works have addressed hypoxia-induced changes in intestinal transport.The effects of cyclooxygenase blockade with indomethacin on short-circuit current (Isc) and oxygen consumption(QO2) of the distal colonic epithelium ofcontrol rats and rats submitted to hypoxia for 10 days at 0.52 atm were studied. Isolated mucosae weremounted in an Ussing chamber modified for measuring QO2 while preserving transepithelial vectorial transport. Amiloride was added to the mucosal hemichamber to block a sodium component of Isc present in hypoxic rats. In this condition, basal Isc did not differ between the hypoxic and the control group, but QO2 was higher in the former. Indomethacin (30 ýmol/L)reduced Isc to the same extent in both groups, but QO2 reduction was larger in the hypoxic group. Pharmacologicalblockade of chloride secretion and a low-chloride solution abolished the indomethacin-induced reductionsof Isc in both groups, and the reduction of QO2 in controls, and attenuated but did not suppress the QO2 reduction in the hypoxic group. Linear regressionanalysis of QO2 changes versus Isc changes yielded a significant correlation for both groups, with regression lines with the same slope, but a higher position in hypoxic hypoxic animals. Results suggest that spontaneously released prostaglandins are equally important for maintaining colonic chloride secretion in hypoxic as in normoxic rats, but that, in the former, indomethacin has an additional effect on QO2 which is unrelated to ion transport.(AU)
La hipoxia hipobárica crónica es un estresante ambiental fisiológico. Aunque sus efectos se han estudiado en lamayoría de los sistemas orgánicos, hay pocos trabajos sobre su influencia en el transporte intestinal. Se estudió el efecto del bloqueo de la ciclooxigenasa con indometacina sobre la corriente de cortocircuito (Isc), el consumo de oxígeno (QO2) del epitelio del colon distal de ratas controles y fueron sometidas a hipoxia durante 10 díasa 0,52 atm. Se montaron preparados de mucosa aislada en una cámara de Ussing modificada para medir QO2 preservando el transporte vectorial transepitelial. Se añadió amilorida a la hemicámara mucosa para bloquear un componente de la Isc debido al sodio presente en ratas hipóxicas. En esta condición, la Isc basal fue similar en ambos grupos, pero el QO2 fue mayor enlos controles. La indometacina (30 mmol/L) redujo igualmente la Isc en ambos grupos; siendo la disminuciónde QO2 mayor en el hipóxico. El bloqueo de la secreció de cloruro (farmacológico y por omisión del ión) suprimió la disminución de Isc en ambos grupos y deQO2 en el control, y redujo, sin abolir, la disminución de QO2 en el hipóxico. El análisis de regresión lineal de cambios en QO2 versus cambios en Isc mostró en ambos grupos correlación significativa con líneas de regresiónde igual pendiente, pero más alta en el hipóxico. Los resultados sugieren que las prostaglandinas liberadas espontáneamente son igualmente importantes en mantener la secreción de cloruro en ratas hipóxicas y normóxicas,pero en las primeras la indometacina tiene además un efecto depresor del QO2 no relacionado con el transporte iónico.(AU)
Assuntos
Animais , Masculino , Ratos , Consumo de Oxigênio/efeitos dos fármacos , Indometacina/farmacologia , Hipóxia/metabolismo , Colo/efeitos dos fármacos , Ratos Wistar , Consumo de Oxigênio/fisiologia , Indometacina/metabolismo , Colo/metabolismo , Modelos Animais de DoençasRESUMO
Chronic hypobaric hypoxia is a physiological environmental stressor. While its effects on most major organsystems have been extensively studied, few works have addressed hypoxia-induced changes in intestinal transport.The effects of cyclooxygenase blockade with indomethacin on short-circuit current (Isc) and oxygen consumption(QO2) of the distal colonic epithelium ofcontrol rats and rats submitted to hypoxia for 10 days at 0.52 atm were studied. Isolated mucosae weremounted in an Ussing chamber modified for measuring QO2 while preserving transepithelial vectorial transport. Amiloride was added to the mucosal hemichamber to block a sodium component of Isc present in hypoxic rats. In this condition, basal Isc did not differ between the hypoxic and the control group, but QO2 was higher in the former. Indomethacin (30 ìmol/L)reduced Isc to the same extent in both groups, but QO2 reduction was larger in the hypoxic group. Pharmacologicalblockade of chloride secretion and a low-chloride solution abolished the indomethacin-induced reductionsof Isc in both groups, and the reduction of QO2 in controls, and attenuated but did not suppress the QO2 reduction in the hypoxic group. Linear regressionanalysis of QO2 changes versus Isc changes yielded a significant correlation for both groups, with regression lines with the same slope, but a higher position in hypoxic hypoxic animals. Results suggest that spontaneously released prostaglandins are equally important for maintaining colonic chloride secretion in hypoxic as in normoxic rats, but that, in the former, indomethacin has an additional effect on QO2 which is unrelated to ion transport.
La hipoxia hipobárica crónica es un estresante ambiental fisiológico. Aunque sus efectos se han estudiado en lamayoría de los sistemas orgánicos, hay pocos trabajos sobre su influencia en el transporte intestinal. Se estudió el efecto del bloqueo de la ciclooxigenasa con indometacina sobre la corriente de cortocircuito (Isc), el consumo de oxígeno (QO2) del epitelio del colon distal de ratas controles y fueron sometidas a hipoxia durante 10 díasa 0,52 atm. Se montaron preparados de mucosa aislada en una cámara de Ussing modificada para medir QO2 preservando el transporte vectorial transepitelial. Se añadió amilorida a la hemicámara mucosa para bloquear un componente de la Isc debido al sodio presente en ratas hipóxicas. En esta condición, la Isc basal fue similar en ambos grupos, pero el QO2 fue mayor enlos controles. La indometacina (30 mmol/L) redujo igualmente la Isc en ambos grupos; siendo la disminuciónde QO2 mayor en el hipóxico. El bloqueo de la secreció de cloruro (farmacológico y por omisión del ión) suprimió la disminución de Isc en ambos grupos y deQO2 en el control, y redujo, sin abolir, la disminución de QO2 en el hipóxico. El análisis de regresión lineal de cambios en QO2 versus cambios en Isc mostró en ambos grupos correlación significativa con líneas de regresiónde igual pendiente, pero más alta en el hipóxico. Los resultados sugieren que las prostaglandinas liberadas espontáneamente son igualmente importantes en mantener la secreción de cloruro en ratas hipóxicas y normóxicas,pero en las primeras la indometacina tiene además un efecto depresor del QO2 no relacionado con el transporte iónico.
Assuntos
Animais , Masculino , Ratos , Hipóxia/metabolismo , Colo/efeitos dos fármacos , Indometacina/farmacologia , Consumo de Oxigênio/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Indometacina/metabolismo , Consumo de Oxigênio/fisiologia , Ratos WistarRESUMO
Epithelial ion transport is dependent on ATP supply provided by aerobic metabolism. In the rat distal colon chloride secretion accounts for the largest portion of electrogenic transport measured as the short-circuit current (I(SC)). Inhibition of basal chloride secretion decreases epithelial oxygen consumption (QO2) in this tissue, while serotonin (5-hydroxytryptamine) proportionally increases both Isc and QO2. The effect of serotonin in this tissue is mainly mediated by 5HT4 receptors linked to adenylate cyclase through a stimulant G protein (GS). This work assessed whether the chloride secretion-induced increase in QO2 is a common characteristic of secretagogues, which act through either cAMP-dependent or Ca(2+)-dependent mechanisms. The effects of phosphodiesterase inhibitor 3-isobutyl-1-methylxantine (IBMX) and muscarinic agonist carbachol (both 0.1 mmol/L) were studied in rat distal colon isolated mucosa mounted in an Ussing chamber adapted for continuous measurement of oxygen concentration, allowing determination of QO2. Baseline I(SC) and QO2 were compared with I(SC) and QO2 after addition of either serotonin as an active control, IBMX, carbachol or IBMX plus carbachol. Each drug increased proportionally Isc and QO2. Although the effect of IBMX alone was modest and that of carbachol was short-lived, a synergic effect on Isc and QO2 was seen when both drugs were simultaneously added. Linear regression analysis showed a significant correlation between increases in I(SC) and QO2 (r2 = 0.746; P < 0.0001). Thus, stimulation of chloride secretion increases QO2 regardless of the intracellular pathway involved. These results extend previous findings, corroborating the close coupling between chloride secretion and QO2 in this epithelium.
Assuntos
Cálcio/metabolismo , Cloretos/metabolismo , Colo/metabolismo , AMP Cíclico/metabolismo , Consumo de Oxigênio/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , Animais , Carbacol/farmacologia , Interações Medicamentosas , Mucosa Intestinal/metabolismo , Masculino , Agonistas Muscarínicos/farmacologia , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
El transporte iónico epitelial exige aporte de ATP provisto por el metabolismo aeróbico. En el colon distal de rata, la secreción de cloruro explica la mayor parte del transporte electrogénico medido como corriente de cortocircuito (ISC). La inhibición de la secreción basal de cloruro reduce el consumo epitelial de oxígeno (QO2), mientras que la serotonina aumenta proporcionalmente ISC y QO2. El efecto de la serotonina es mediado por receptores 5HT4 acoplados a adenilato ciclasa medianteproteína G estimulante (GS). En este trabajo seestudió si el aumento del QO2 asociado con la secreción de cloruro es un efecto común a otros agentes que actúan sobre cAMP o Ca2+. Los efectos del inhibidor de la fosfodiesterasa, 3-isobutil-1-metilxantina (IBMX) y del agonista muscarínico carbacol (ambos a 0.1 mmol/L) se evaluaron en la mucosa aislada del colon distal de rata montado en una cámara de Ussing modificada para determinación continua de la concentración de oxígeno, permitiendo medir QO2. Se compararon la ISC y el QO2 basales con las resultantes del añadido de serotonina (control activo), IBMX, carbacol, o IBMX y carbacol. Todos aumentaron proporcionalmente ISC y QO2. Aunque el efecto de IBMX solo fue modesto y el del carbacol fue breve, se observó una sinergia cuando fueron agregados simultáneamente. El análisis de regresión lineal mostró una correlación significativa entre los incrementos de ISC y de QO2 (r2 = 0.746; P menor que 0.0001). Por tanto, la estimulación de la secreción de cloruro aumenta el QO2 independientemente de la vía efectora intracelular involucrada. Estos resultados corroboran el estrecho acoplamiento entre secreción de cloruro y QO2 en este epitelio. (AU)
Assuntos
Animais , Masculino , Ratos , RESEARCH SUPPORT, NON-U.S. GOVT , Consumo de Oxigênio/fisiologia , Cálcio/metabolismo , AMP Cíclico/metabolismo , Cloretos/metabolismo , Colo/metabolismo , Agonistas Muscarínicos/farmacologia , Serotonina/farmacologia , Carbacol/farmacologia , Mucosa Intestinal/metabolismo , Interações Medicamentosas , Ratos WistarRESUMO
Epithelial ion transport is dependent on ATP supply provided by aerobic metabolism. In the rat distal colon chloride secretion accounts for the largest portion of electrogenic transport measured as the short-circuit current (I(SC)). Inhibition of basal chloride secretion decreases epithelial oxygen consumption (QO2) in this tissue, while serotonin (5-hydroxytryptamine) proportionally increases both Isc and QO2. The effect of serotonin in this tissue is mainly mediated by 5HT4 receptors linked to adenylate cyclase through a stimulant G protein (GS). This work assessed whether the chloride secretion-induced increase in QO2 is a common characteristic of secretagogues, which act through either cAMP-dependent or Ca(2+)-dependent mechanisms. The effects of phosphodiesterase inhibitor 3-isobutyl-1-methylxantine (IBMX) and muscarinic agonist carbachol (both 0.1 mmol/L) were studied in rat distal colon isolated mucosa mounted in an Ussing chamber adapted for continuous measurement of oxygen concentration, allowing determination of QO2. Baseline I(SC) and QO2 were compared with I(SC) and QO2 after addition of either serotonin as an active control, IBMX, carbachol or IBMX plus carbachol. Each drug increased proportionally Isc and QO2. Although the effect of IBMX alone was modest and that of carbachol was short-lived, a synergic effect on Isc and QO2 was seen when both drugs were simultaneously added. Linear regression analysis showed a significant correlation between increases in I(SC) and QO2 (r2 = 0.746; P < 0.0001). Thus, stimulation of chloride secretion increases QO2 regardless of the intracellular pathway involved. These results extend previous findings, corroborating the close coupling between chloride secretion and QO2 in this epithelium.
RESUMO
El transporte iónico epitelial exige aporte de ATP provisto por el metabolismo aeróbico. En el colon distal de rata, la secreción de cloruro explica la mayor parte del transporte electrogénico medido como corriente de cortocircuito (ISC). La inhibición de la secreción basal de cloruro reduce el consumo epitelial de oxígeno (QO2), mientras que la serotonina aumenta proporcionalmente ISC y QO2. El efecto de la serotonina es mediado por receptores 5HT4 acoplados a adenilato ciclasa medianteproteína G estimulante (GS). En este trabajo seestudió si el aumento del QO2 asociado con la secreción de cloruro es un efecto común a otros agentes que actúan sobre cAMP o Ca2+. Los efectos del inhibidor de la fosfodiesterasa, 3-isobutil-1-metilxantina (IBMX) y del agonista muscarínico carbacol (ambos a 0.1 mmol/L) se evaluaron en la mucosa aislada del colon distal de rata montado en una cámara de Ussing modificada para determinación continua de la concentración de oxígeno, permitiendo medir QO2. Se compararon la ISC y el QO2 basales con las resultantes del añadido de serotonina (control activo), IBMX, carbacol, o IBMX y carbacol. Todos aumentaron proporcionalmente ISC y QO2. Aunque el efecto de IBMX solo fue modesto y el del carbacol fue breve, se observó una sinergia cuando fueron agregados simultáneamente. El análisis de regresión lineal mostró una correlación significativa entre los incrementos de ISC y de QO2 (r2 = 0.746; P menor que 0.0001). Por tanto, la estimulación de la secreción de cloruro aumenta el QO2 independientemente de la vía efectora intracelular involucrada. Estos resultados corroboran el estrecho acoplamiento entre secreción de cloruro y QO2 en este epitelio.
Epithelial ion transport is dependent on ATP supply provided by aerobic metabolism. In the rat distal colon chloride secretion accounts for the largest portion of electrogenic transport measured as the short-circuit current (ISC). Inhibition of basal chloride secretion decreases epithelial oxygen consumption (QO2) in this tissue, while serotonin (5-hydroxytryptamine) proportionally increases both Isc and QO2. The effect of serotonin in this tissue is mainly mediated by 5HT4 receptors linked to adenylate cyclase through a stimulant G protein (GS). This work assessed whether the chloride secretion-induced increase in QO2 is a common characteristic of secretagogues, which act through either cAMP-dependent or Ca2+-dependent mechanisms. The effects of phosphodiesterase inhibitor 3-isobutyl-1- methylxantine (IBMX) and muscarinic agonist carbachol (both 0.1 mmol/L) were studied in rat distal colon isolated mucosa mounted in an Ussing chamber adapted for continuous measurement of oxygen concentration, allowing determination of QO2. Baseline ISC and QO2 were compared with ISC and QO2 after addition of either serotonin as an active control, IBMX, carbachol or IBMX plus carbachol. Each drug increased proportionally Isc and QO2. Although the effect of IBMX alone was modest and that of carbachol was short-lived, a synergic effect on Isc and QO2 was seen when both drugs were simultaneously added. Linear regression analysis showed a significant correlation between increases in ISC and QO2 (r2 = 0.746; P < 0.0001). Thus, stimulation of chloride secretion increases QO2 regardless of the intracellular pathway involved. These results extend previous findings, corroborating the close coupling between chloride secretion and QO2 in this epithelium
Assuntos
Animais , Masculino , Ratos , Cálcio/metabolismo , Cloretos/metabolismo , Colo/metabolismo , AMP Cíclico/metabolismo , Consumo de Oxigênio/fisiologia , Carbacol/farmacologia , Interações Medicamentosas , Mucosa Intestinal/metabolismo , Agonistas Muscarínicos/farmacologia , Ratos Wistar , Serotonina/farmacologiaRESUMO
The aerobic metabolic cost of chloride secretion was studied in rat distal colon isolated mucosa under several conditions by simultaneous measurement of short-circuit current and oxygen consumption under conditions that preserve vectorial ion transport. A low-chloride solution and the presence of bumetanide plus diphenylamine-2-carboxylate reduced short-circuit current by 75% and oxygen consumption by 25%. Ouabain decreased short-circuit current by 93% and oxygen consumption by 32%. Serotonin increased both variables by 59% and 33%, respectively. Bumetanide and diphenylamine-2-carboxylate reduced but did not abolish the effect of serotonin on short-circuit current and oxygen consumption. Changes in short-circuit current and oxygen consumption were linearly correlated under all conditions tested. It is concluded that, in the unstimulated rat distal colon epithelium, chloride secretion accounts for about 75% of ouabain-sensitive short-circuit current and oxygen consumption. Stimulated chloride secretion may demand over 40% of total oxygen consumption.
Assuntos
Cloretos/metabolismo , Colo/metabolismo , Mucosa Intestinal/metabolismo , Consumo de Oxigênio , Animais , Técnicas In Vitro , Masculino , Ouabaína/farmacologia , Consumo de Oxigênio/fisiologia , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
Chronic hypoxia induces many physiological changes, but little is known about its effects on colonic epithelial function. Isolated distal colon mucosa from rats under normobaric conditions and rats submitted to hypobaric hypoxia for either 4 or 10 days was studied in an Ussing chamber. After 4 days of hypoxia, there was only a 15% increase in transepithelial resistivity. However, 10-day hypoxic rats showed higher short circuit current, potential difference, and resistivity. In this group, but not in normal or 4-day hypoxic animals, amiloride dose-dependently depressed short circuit current. The response to acute hypoxia in vitro was unchanged after chronic hypoxia and was not affected by amiloride. Although the amiloride-sensitive increase in short circuit current in 10-day hypoxic rats might resemble mineralocorticoid action, resistivity was increased and serum aldosterone was very low. It is suggested that chronic hypoxia may enhance electrogenic sodium transport by an aldosterone-independent mechanism.
Assuntos
Amilorida/farmacologia , Pressão Atmosférica , Colo/efeitos dos fármacos , Colo/fisiopatologia , Hipóxia/fisiopatologia , Animais , Técnicas In Vitro , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/fisiopatologia , Masculino , Ratos , Ratos WistarRESUMO
En el presente trabajo se propone un nuevo modelo experimental para la autoperfusión del nódulo sinusal canino, basado en el originalmente descripto por James y Nadeau, con modificaciones que, a nuestro juicio, lo hacen más ventajoso. Se realizó un cortocircuito entre las arterias mamaria interna y auricular dorsal derecha. Esta última, en un 82% de los perros, es la arteria dominante en la irrigación del nódulo. Midiendo la velocidad de avance del colorante se calculó el flujo sanguíneo del cortocircuito, que fue de 2.5ñ0.15 ml/m. Cuando se inyectaron en el "by-pass" tanto isoproterenol como verapamil, se produjeron rápidos cambios en la frecuencia cardíaca, sin que se observaran modificaciones apreciables en el comportamiento eléctrico del resto del miocardio. Ello se puede constatar a través del electrocardiograma y de los registros endocavitarios. Este modelo de autoperfusión sinusal deja la circulación coronaria intacta, a diferencia de James y Nadeau, que introduce el catéter en la arteria coronaria derecha. El cortocircuito intratorácico reduce la pérdida de calor y disminuye la posibilidad de aparición de coágulos dentro del catéter. El modelo es apropiado tambíen para estudios experimentales crónicos (AU)
Assuntos
Cães , Animais , Masculino , Feminino , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/farmacologia , Nó Sinoatrial/fisiologia , Verapamil/farmacologia , Artéria Torácica Interna/cirurgia , Artérias/cirurgia , Cateterismo Cardíaco , Perfusão/métodosRESUMO
En el presente trabajo se propone un nuevo modelo experimental para la autoperfusión del nódulo sinusal canino, basado en el originalmente descripto por James y Nadeau, con modificaciones que, a nuestro juicio, lo hacen más ventajoso. Se realizó un cortocircuito entre las arterias mamaria interna y auricular dorsal derecha. Esta última, en un 82% de los perros, es la arteria dominante en la irrigación del nódulo. Midiendo la velocidad de avance del colorante se calculó el flujo sanguíneo del cortocircuito, que fue de 2.5ñ0.15 ml/m. Cuando se inyectaron en el "by-pass" tanto isoproterenol como verapamil, se produjeron rápidos cambios en la frecuencia cardíaca, sin que se observaran modificaciones apreciables en el comportamiento eléctrico del resto del miocardio. Ello se puede constatar a través del electrocardiograma y de los registros endocavitarios. Este modelo de autoperfusión sinusal deja la circulación coronaria intacta, a diferencia de James y Nadeau, que introduce el catéter en la arteria coronaria derecha. El cortocircuito intratorácico reduce la pérdida de calor y disminuye la posibilidad de aparición de coágulos dentro del catéter. El modelo es apropiado tambíen para estudios experimentales crónicos
Assuntos
Cães , Animais , Masculino , Feminino , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/farmacologia , Nó Sinoatrial/fisiologia , Verapamil/farmacologia , Artéria Torácica Interna/cirurgia , Artérias/cirurgia , Cateterismo Cardíaco , Perfusão/métodosRESUMO
Se compararon los valores de los parametros electrocardiograficos, obtenidos en ratas sometidas previamente a hipoxia hipobarica cronica (GII), con los de los animales del grupo control (GI), mantenidos a presion ambiente. Durante los registros ambos grupos de ratas eran ventilados primero con aire y luego con una mezcla pobre en oxigeno. El grupo GII, durante la respiracion con aire, mostro un incremento de los intervalos QT y QaT y una disminucion de la frecuencia cardiaca espontanea. Durante la ventilacion con la mezcla pobre en oxigeno, en ambos grupos se observo una prolongacion del intervalo PR que condujo a un bloqueo AV de 2o grado, de aparicion mas tardia en GII. La hipoxia aguda produjo una disminucion del QT en todos los animales y un aumento del QRS solamente en los adaptados. Estos resultados muestran que la hipoxia hipobarica cronica prolonga la repolarizacion ventricular. La hipoxia aguda aumenta la velocidad de repolarizacion en ambos grupos, pero en el GII permanece prolongada respecto al valor alcanzado en GI. Este ultimo hecho podria interpretarse como el desarrollo de un mecanismo de adaptacion inducido por la hipoxia hipobarica cronica
Assuntos
Masculino , Feminino , Animais , Ratos , Adaptação Fisiológica , Hipóxia , EletrocardiografiaRESUMO
Se compararon los valores de los parametros electrocardiograficos, obtenidos en ratas sometidas previamente a hipoxia hipobarica cronica (GII), con los de los animales del grupo control (GI), mantenidos a presion ambiente. Durante los registros ambos grupos de ratas eran ventilados primero con aire y luego con una mezcla pobre en oxigeno. El grupo GII, durante la respiracion con aire, mostro un incremento de los intervalos QT y QaT y una disminucion de la frecuencia cardiaca espontanea. Durante la ventilacion con la mezcla pobre en oxigeno, en ambos grupos se observo una prolongacion del intervalo PR que condujo a un bloqueo AV de 2o grado, de aparicion mas tardia en GII. La hipoxia aguda produjo una disminucion del QT en todos los animales y un aumento del QRS solamente en los adaptados. Estos resultados muestran que la hipoxia hipobarica cronica prolonga la repolarizacion ventricular. La hipoxia aguda aumenta la velocidad de repolarizacion en ambos grupos, pero en el GII permanece prolongada respecto al valor alcanzado en GI. Este ultimo hecho podria interpretarse como el desarrollo de un mecanismo de adaptacion inducido por la hipoxia hipobarica cronica