RESUMEN
1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of L-arginine during extracellular fluid volume expansion (10% bodyweight). 2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: L-arginine (250 mg/kg, i.v.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.v.), haloperidol (3 mg/kg, i.p.) and L-arginine + haloperidol (n = 8). Mean arterial pressure (MAP), diuresis, natriuresis, kaliuresis, glomerular filtration rate, renal plasma flow (RPF) and nitrite and nitrate (NO(x)) excretion were determined. 3. The increase in MAP induced by L-NAME was greater in expanded than in non-expanded rats (42 +/- 3 vs 32 +/- 3 mmHg, respectively; P < 0.01). Administration of haloperidol did not modify the L-arginine hypotensive effect. 4. Blockade of nitric oxide synthase diminished urine flow in non-expanded (4.15 +/- 0.56 vs 0.55 +/- 0.11 microL/min per 100 g; P < 0.01) and expanded animals (24.42 +/- 3.67 vs 17.85 +/- 2.16 microL/min per 100 g; P < 0.01). Diuresis induced by L-arginine was reduced by DA blockade in both non-expanded (17.15 +/- 2.11 vs 6.82 +/- 0.61 microL/min per 100 g; P < 0.01) and expanded animals (44.26 +/- 8.45 vs 25.43 +/- 5.12 microL/min per 100 g; P < 0.01). 5. Sodium excretion decreased with L-NAME treatment in non-expanded (0.22 +/- 0.03 vs 0.06 +/- 0.01 microEq/min per 100 g; P < 0.01) and expanded animals (3.72 +/- 0.70 vs 1.89 +/- 0.23 microEq/min per 100 g; P < 0.01). Natriuresis induced by L-arginine was diminished by haloperidol both in non-expanded (0.94 +/- 0.13 vs 0.43 +/- 0.04 microEq/min per 100 g; P < 0.01) and expanded rats (12.77 +/- 0.05 vs 3.53 +/- 0.75 microEq/min per 100 g; P < 0.01). Changes in kaliuresis changes seen following treatment with L-arginine, L-NAME and L-arginine + haloperidol followed a pattern similar to that observed for sodium excretion in both groups of rats. 6. L-arginine enhanced RPF in non-expanded animals (11.96 +/- 0.81 vs 14.52 +/- 1.05 mL/min per 100 g; P < 0.01). Glomerular filtration rate was increased by extracellular volume expansion (3.08 +/- 0.28 vs 5.42 +/- 0.46 mL/min per 100 g; P < 0.01). 7. The increase in NOx induced by acute volume expansion (0.18 +/- 0.03 vs 0.52 +/- 0.08 nmol/min per 100 g; P < 0.01) was diminished following the administration of haloperidol (0.52 +/- 0.08 vs 0.26 +/- 0.06 nmol/min per 100 g; P < 0.01). 8. Although DA does not participate in the actions of nitric oxide on vascular tone, both systems would play an important role in renal function adaptation during extracellular fluid volume expansion.
Asunto(s)
Presión Sanguínea/fisiología , Dopamina/fisiología , Espacio Extracelular/fisiología , Riñón/fisiología , Óxido Nítrico/fisiología , Animales , Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Volumen Sanguíneo/efectos de los fármacos , Volumen Sanguíneo/fisiología , Espacio Extracelular/efectos de los fármacos , Haloperidol/farmacología , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Pruebas de Función Renal/métodos , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/antagonistas & inhibidores , Ratas , Ratas WistarRESUMEN
1. The aim of the present study was to investigate the effects of L-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration of L-Arg in this model. 2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kg L-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR + L-NAME or FUR + L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined. 3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92+/-6 vs 100+/-8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69+/-7 and 76+/-5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration of L-Arg (54+/-3 and 64+/-3 mmHg, respectively). 4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups. 5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME. 6. The combination of L-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33+/-1.68 vs 12.91+/- 0.41 microL/min per 100 g, respectively; volume-expanded rats: 248.5+/-25.4 vs 112,6+/-8.3 microL/min per 100 g, respectively; P < 0.01). 7. The administration of the combination of L-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230+/-0.018 vs 0.45+/-0.03, respectively, P < 0.001; volume-expanded rats: 0.091+/-0.010 vs 0.22+/-0.03, respectively, P < 0.01). 8. The potassium/water excretion rate induced by FUR alone and in the presence of L-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35+/-0.05 vs 0.20+/-0.05 microEq/min per 100 g, respectively; volume-expanded rats: 0.045+/-0.008 vs 0.014+/-0.003 microEq/min per 100 g, respectively; P < 0.01). 9. The decrease in the electrolyte/water excretion ratio observed with FUR + L-Arg in volume-expanded rats was greater than in control animals. 10. The results of the present study show that the administration of FUR with L-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.
Asunto(s)
Arginina/farmacología , Presión Sanguínea/efectos de los fármacos , Diuréticos/farmacología , Espacio Extracelular , Furosemida/farmacología , Riñón/efectos de los fármacos , Animales , Arginina/administración & dosificación , Arginina/fisiología , Diuresis/efectos de los fármacos , Sinergismo Farmacológico , Furosemida/administración & dosificación , Riñón/fisiología , Masculino , Natriuresis/efectos de los fármacos , Potasio/orina , Ratas , Ratas Wistar , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
The aim of the present study was to determine the relationship between the hypotensive effect of the atrial natriuretic peptide (ANP) and the nitric oxide (NO) pathway. N(G)-nitro-L-arginine methyl ester bolus (L-NAME, 1 mg/kg) reverted the decrease in mean arterial pressure induced by ANP administration (5 microg/kg bolus and 0.2 microg x kg(-1) x min(-1) infusion), and the injection of L-NAME before peptide administration suppressed the ANP hypotensive response. To confirm these findings, a histochemical reaction was used to determine NADPH-diaphorase activity (a NO synthase marker) in the endothelium and smooth muscle of aorta and arterioles of the small and large intestine. ANP increased aorta and arteriole endothelium staining after both in vivo administration and in vitro tissue incubation. In both cases, L-NAME prevented the ANP effect on NADPH-diaphorase activity. Tissues incubated with 8-bromoguanosine 3',5'-cyclic monophosphate mimicked ANP action. In addition, ANP administration increased urinary excretion of NO(x) end products. These findings indicate that ANP increases NO synthesis capability and NO production and suggest that the cGMP pathway may be involved. In conclusion, the NO pathway could be an intercellular messenger in the ANP endothelium-dependent vasorelaxation mechanism.
Asunto(s)
Factor Natriurético Atrial/farmacología , Factor Natriurético Atrial/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Óxido Nítrico/fisiología , Animales , Inhibidores Enzimáticos/farmacología , Masculino , NADPH Deshidrogenasa/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Ratas , Ratas WistarRESUMEN
Histochemical reaction of NADPH-diaphorase (NOS-NADPH-d) was used to identify NO synthesis. A 30-min 0.1 microg microg/kg/min ANP infusion led to about a 10% and 35% increase in small and large intestine enterocytes stain respectively. This increase was abolished by a bolus of 1 mg/kg L-NAME before ANP infusion in small intestine, and partially abolished it in colon. Incubation of small and large intestine with 0.5 microM ANP increased stain at about 20%. In both tissues the preincubation with 0.1 mM L-NAME abolished the ANP effect. Incubation with 0.1 mM 8-Br-cGMP enhanced staining about 70% and 30% in small and large intestine respectively. Our results show that ANP enhances NOS-NADPH-d activity, suggesting that ANP stimulates NO synthase in enterocytes by L-arginine-NO pathway. 8-Br-cGMP mimicked the effect of ANP described above. Therefore, the guanylate cyclase-coupled natriuretic receptors, NPR-A and NPR-B, probably mediate this ANP effect.
Asunto(s)
Factor Natriurético Atrial/farmacología , Mucosa Intestinal/efectos de los fármacos , NADPH Deshidrogenasa/análisis , Óxido Nítrico/biosíntesis , Animales , Colon/citología , Colon/efectos de los fármacos , Colon/enzimología , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Guanilato Ciclasa/metabolismo , Histocitoquímica , Procesamiento de Imagen Asistido por Computador , Mucosa Intestinal/citología , Mucosa Intestinal/enzimología , Intestino Delgado/citología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/enzimología , Isoenzimas , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa , Fotoperiodo , Ratas , Ratas Wistar , Receptores del Factor Natriurético Atrial/metabolismoRESUMEN
The aim of the present study was to elucidate the role of an IV dose of endothelin-3 (ET-3) (5 ng Kg-1 min-1) on mean arterial pressure (MAP), on diuresis and natriuresis in control and in volume expanded anesthetized rats. A systemic infusion of ET-3 in normal rats (Group I) increased MAP and produced a trend of increasing diuresis, without changes in natriuresis. A 10% body weight expansion (Group II) increased diuresis and natriuresis without changes in MAP. The simultaneous infusion of ET-3 and expansion with saline (Group III) resulted in an increase in MAP, an enhanced diuretic response, and a natriuresis of similar magnitude to that observed in Group II. These results suggest that the diuresis produced by a low dose of exogenous ET-3 in control rats, is independent of sodium excretion. Furthermore, the enhanced diuresis caused by ET-3 during expansion is greater than the addition of ET-3 and expansion effects, suggesting that new mechanisms are triggered in order to maintain volume and salt homeostasis in this state.
Asunto(s)
Endotelina-3/fisiología , Espacio Extracelular/metabolismo , Sodio/metabolismo , Agua/metabolismo , Animales , Presión Sanguínea/fisiología , Tamaño de la Célula/fisiología , Diuresis/fisiología , Masculino , Natriuresis/fisiología , Ratas , Ratas WistarRESUMEN
In portal hypertensive patients and experimental models, hyperdynamic circulatory disturbances associated to a reduced peripheral resistance and an increased cardiac output appeared. The aim of this research is the study of the baroreflex system behavior partially portal vein ligated-portal hypertensive rats. Sham operated rats (S) (n = 7) and portal hypertensive rats (PH) (n = 9) were used. In anesthetized rats, catheters were introduced into a jugular vein for drug injection and into the ventral tail artery to record blood pressure and heart rate. When rats were conscious and moving freely, a bolus injection of phenylephrine hydrochloride (6 micrograms/kg) was injected in the vein. A sigmoid curve relating systolic blood pressure and heart period was dressed. We analyzed: 1) The gain or sensitivity: the slope of the regression line; 2) The threshold: systolic blood pressure at which the regression begins to be linear. The results were: mean arterial pressure (mmHg): S = 103 +/- 7; PH = 109 +/- 3; gain (ms/mmHg): S = 1.29 +/- 0.10; PH = 0.62 +/- 0.04 (p < 0.001); threshold (mmHg): S = 145 +/- 7; PH = 146 +/- 4. The baroreceptor reflex sensitivity was significantly decreased. No differences appeared in the mean arterial pressure and in the reflex threshold. It is suggested that portal hypertension induces alterations in baroreflex regulation of arterial blood pressure.
Asunto(s)
Barorreflejo/fisiología , Hipertensión Portal/fisiopatología , Animales , Presión Sanguínea/fisiología , Constricción , Modelos Animales de Enfermedad , Modelos Lineales , Masculino , Vena Porta , Ratas , Ratas WistarRESUMEN
Our purpose was to study the influence of the stimulation of the cerebroventricular system on some mechanisms related to hydrosaline equilibrium and blood pressure regulation. Renal function and blood pressure (group 1) as well as the baroreceptor reflex (group 2) were studied. In group 1, we measured diuresis, natriuresis, creatinine clearance, lithium clearance, and blood pressure in control rats and after stimulation of the cerebroventricular system with 1 M NaCl solution. In group 2, we evaluated the baroreceptor reflex, producing an increase of blood pressure with an injection of phenylephrine to obtain baroreceptor reflex curves--characterized by threshold, point of inflection, heart period range, gain, and systolic pressure corresponding to half the heart period range (SBP50)--in control and experimental rats injected with saline and 1 M NaCl solution, respectively. In group 1 experimental rats, we observed a significant increase in diuresis, natriuresis, blood pressure, and glomerular filtration rate. A substantial increase was also registered in sodium filtered load and reabsorbed sodium in the proximal convoluted tubule and distal nephron. No differences were observed either in fractional proximal tubule or in distal nephron sodium reabsorption. In group 2 experimental rats, mean arterial blood pressure, threshold, point of inflection, and SBP50 were significantly higher than in control rats. By contrast, a decrease in gain and heart period range was observed. No difference was obtained in heart rate. Our results demonstrate that the increase of the natriuresis is due, at least in part, to an increase in sodium filtered load.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Riñón/fisiología , Presorreceptores/fisiología , Reflejo/fisiología , Cloruro de Sodio/administración & dosificación , Absorción , Animales , Presión Sanguínea/efectos de los fármacos , Diuresis/efectos de los fármacos , Tasa de Filtración Glomerular , Frecuencia Cardíaca , Inyecciones Intraventriculares , Riñón/efectos de los fármacos , Túbulos Renales/metabolismo , Masculino , Natriuresis/efectos de los fármacos , Presorreceptores/efectos de los fármacos , Ratas , Reflejo/efectos de los fármacos , Sodio/metabolismoRESUMEN
The aim of the investigation was to evaluate the effects of the intracerebroventricular (ICV) injection of 0.1 ml of 1 M NaCl, on the body water distribution in nephrectomized male rats. In comparison with the control rats injected with an equal volume of isotonic saline, the ICV injection of 1 M NaCl elicited 90 min later a significant increase of plasma volume whereas the total water, the inulin space, the calculated interstitial space and the intracellular water were not altered. The increase of plasma volume could be explained by a decrease of capillary efflux to the interstitial space. These results suggest that the ICV injection of 1 M NaCl releases a substance which could regulate the plasma volume.
Asunto(s)
Factor Natriurético Atrial/farmacología , Agua Corporal/metabolismo , Cloruro de Sodio/administración & dosificación , Animales , Inyecciones Intraventriculares , Masculino , Ratas , Ratas EndogámicasRESUMEN
In the rat, the effects of an atrial natriuretic factor (ANF) (Rat, 8-33 Peninsula Lab) on body water distribution have been evaluated. The ANF administration to nephrectomized animals produced a decrease in plasma volume and a slight increase in haematocrit and in plasma albumin concentration. No modifications were observed in total and intracellular water. The fluid efflux from the capillaries appeared to be located in the interstitial space. These results suggest that ANF could regulate plasma volume and systemic blood pressure, concurrently with its other known effects.
Asunto(s)
Factor Natriurético Atrial/fisiología , Agua Corporal/fisiología , Equilibrio Hidroelectrolítico , Animales , Presión Sanguínea , Volumen Sanguíneo , Espacio Extracelular/fisiología , Hematócrito , Masculino , Nefrectomía , RatasRESUMEN
Baroreflex control of cardiovascular parameters was studied in control, atropine- and guanethidine-treated rats. Baroreceptor activity was tested by the relationship between the increase in blood pressure produced by a phenylephrine administration (bolus ov infusion) and the induced bradycardia. No differences were observed in basal arterial blood pressure and heart rate between treated- and control rats. Baroreceptor sensitivity was lower in atropine- or guanethidine-treated rats than in control animals. Baroreceptor activity has two components: a first, rapid, predominantly parasympathetic and a second, slower, that is mediated by both parasympathetic and sympathetic efferent pathways.
Asunto(s)
Presión Sanguínea , Presorreceptores/fisiología , Animales , Derivados de Atropina/farmacología , Presión Sanguínea/efectos de los fármacos , Guanetidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Fenilefrina/farmacología , Presorreceptores/efectos de los fármacos , Ratas , Ratas Endogámicas , Nervio Vago/efectos de los fármacosRESUMEN
The overall open-loop gain of the rapidly acting arterial pressure control system was estimated in rats. Wistar male animals were bled by 6 ml/kg body weight. The open-loop gain of the rapidly acting arterial pressure control system was estimated as the relation between the fall of arterial pressure produced by the haemorrhage and the difference between control arterial pressure and the steady state reached after the recovery of the haemorrhage. The results observed suggest that the rapidly acting arterial pressure control system is less developed in the rat than in others Mammals.