Summary The effect of the nitrogen content of the diet on ammonia detoxication in rats was studied using 6 diets containing 5, 15 and 70% casein with or without 2% NH4Cl. Evaluation of ammonia detoxication was based on the estimation of the LD50 of intraperitoneally administered NH4Cl, on the levels of ammonia, urea and glucose in blood, and on the arginase, δ‐ornithine transaminase and ornithine transcarbamylase activities in the liver and on ATP + ADP concentration in the liver, kidneys and muscles. Higher doses of exogenous ammonia were tolerated by rats receiving for some time a protein‐rich diet or a diet containing an ammonium salt as an additive. The faster rate of ammonia detoxication in such cases was due to faster urea synthesis resulting from increased amounts of substrate and available energy. The effect of changes in the activity of the ornithine cycle enzymes was probably less important. The observed considerable increase of the ATP + ADP level in the muscles of rats receiving increased amounts of dietary nitrogen suggests that muscles are involved in the process of ammonia detoxication. Zusammenfassung Der Einfluß des Gehaltes an Eiweiß und NH4Cl im Futter auf die Ammoniak‐Entgiftung bei Ratten Bei Ratten wurde der Einfluß des Stickstoffgehaltes des Futters (5, 15 und 70% Kasein im Futter) sowie der Zugabe von NH4Cl zum Futter auf die Ammoniak‐Entgiftung untersucht. Die Beurteilung der Ammoniak‐Entgiftung basierte auf folgenden Parametern: LD50 bei intraperitoneal verabreichtem NH4Cl; Gehalt des Blutes an Ammoniak, Harnstoff und Glucose; Aktivitäten der Arginase, δ‐Ornithin‐Transaminase und Ornithin‐Transcarbamylase der Leber; ATP‐ und ADP‐Konzentration in Leber, Niere und Muskulatur. Ratten, welche eine proteinreiche Diät oder eine Diät mit Ammoniumsalz‐Zusatz erhielten, ertrugen höhere Mengen von exogenem Ammoniak. Die größere Detoxikationsrate war auf die intensivere Harnstoffsynthese zurückzuführen. Diese beruhte ihrerseits auf einer höheren Substratkonzentration sowie einer erhöhten Energiefreisetzung. Aktivitätsänderungen der Enzyme des Ornithinzyklus spielten wahrscheinlich eine geringere Rolle. Die ATP‐ und ADP‐Vermehrung in der Muskulatur der Tiere, welche zunehmend höhere Stickstoffmengen im Futter erhielten spricht dafür, daß die Muskulatur bei der Ammoniak‐Entgiftung mitbeteiligt ist. Résumé Influence de la teneur en protéines et en NH4Cl dans la nourriture sur la désintoxication ammoniacale chez le rat On a examiné l'influence de la teneur en azote (5,15 et 70% de caséine dans l'aliment) et l'addition de NH4Cl dans la nourriture sur la d'sintoxication ammoniacale. L'analyse de désintoxication ammoniacale s'est basée sur les paramètres suivants: LD50 lors d'application intrapéritonéale de NH4Cl; teneur du sang en ammoniac, en urée et en glucose; activités de l'arginase, de δ‐ornithine‐transaminase et de l'ornithine‐transcarbamylase du foie; concentration en ATP et ADP dans le foie, les reins et la musculature. Les rats ayant reçu une alimentation riche en protéines ou avec addition de s...
Using the 133Xe clearance method it is shown that NH4Cl infusion into the anterior mesenteric vein decreased capillary blood flow in the liver. Phentolamine completely and propranolol partially prevented the depressive action of NH4Cl on hepatic blood flow. NH4Cl infused into the jugular vein provoked a slight increase in the hepatic blood flow. The adrenaline-like action of ammonium ion on the blood circulation in the liver region is discussed.Blood flow in the vessels of the portal system in ruminants has been the topic of only a few reports [reviewed by Webster, 1974] despite the peculiarity of the digestive processes in these animals. Sellers, Stevens and McLeod [1964] and Sellers [1965] showed that the increased concentration of volatile fatty acids as well as CO2 in the rumen fluid caused a con)siderable rise of blood flow iln the rumen wall. The portal blood flow increased proportionally to the amount of metabolizable energy intake in the feed [Webster and White, 1973]. Weekes and Webster [1975] also confirmed the stimulating influence of volatile fatty acids on blood flow through the liver.Since ammonium ion has been recognized as an adrenaline-like agent in the regulation of tissue metabolism [Prior, Cliford, Gibson and Visek, 1971, Wiechetek, Garwacki andBarej, 1975] one could expect its depressive influence on the blood circulation in the liver. However, the influence of dietary protein level on the blood flow in the portal vein could not be assessed [Webster, 1974]. It seems that in normal conditions of digestion the influence of rumen volatile fatty acids dominates the regulation of physiological processes in this region.Therefore in the present paper we attempted to evaluate changes in the blood flow through the liver of sheep loaded with ammonium chloride through the portal vein and jugular vein. Simultaneously the pharmacological blockade of alpha and beta adrenergic receptors has been used for estimation of the adrenaline-like action of ammonia on the hepatic circulation.99
Summary The 133Xe bolus technique was used for nutritive hepatic blood flow estimation in sheep. The tracer was injected into the portal vein and the radioactivity was monitored externally by a γ‐scintillation detector. Blood flow was calculated from the initial slope of the semilogarithmically plotted washout curve. The partition coefficient (λ) between blood and hepatic tissue for 133Xe was found to be 0.70 ml./g. Zusammenfassung Messung der Durchstömung der Leber mit Pfortaderblut bei Schafen mittels der 133Xe‐Bolustechnik Zur Bestimmung der Durchströmung der Leber mit Pfortaderblut bei Schafen wurde die 133Xe‐Bolustechnik verwendet. Das Isotop wurde in die Pfortader injiziert und die Radioaktivität mit einem γ‐Szintillations‐Detektor extern registriert. Die Blutstromstärke wurde aus der initialen Neigung der semilogarithmisch aufgezeichneten Auswaschungskurve berechnet. Für den Teilungskoeffizient (λ) des 133Xe zwischen dem Blut und Lebergewebe wurde ein Wert von 0,70 ml/g gefunden. Résumé Mesure de l'irrigation hépatique par le sang de la vein porte chez des moutons au moyen de la technique 133Xe‐Bolus La technique 133Xe‐Bolus a été utilisée pour déterminer l'irrigation du foie par le sang de la veine porte chez des moutons. L'isotope a été injecté dans la veine porte et la radioactivité a été enregistrée extérieurement avec un détecteur à scintillations γ. L'intensité de la circulation sanguine a été calculée sur la base de l'inclinaison initiale de la courbe logarythmique croissante indiquée. Une valuer de 0,70 ml/g a été trouvée pour le coefficient de séparation (λ) de 133Xe entre le sang et le tissu hépatique. Resumen Medición de la perfusión hepática con sangre portal en ovejas siguiendo la técnica del bolo y 133Xe Para valorar la perfusión del hígado con sangre portal en ovejas, se empleó la técnica del bolo y 133Xe. El isótopo fué inyectado en la vena porta, registrándose externamente la radiactividad con un detector de escincilaciones γ. Se calculó el vigor del torrente circulatorio a partir del declive inicial de la curva de lavado registrada semilogarítmicamente. Se halló para el coeficiente partitivo (λ) del 133Xe entre la sangre y el tejido hepático un valor de 0.70 ml./g.
Summary The synthesis, blood plasma turnover and urinary excretion of the orotic acid in normo‐ and hyperargininaemic sheep was investigated. The whole‐body orotate formation was evaluated indirectly by the measurement of urinary orotate excretion after blockage of pyrimidine pathway with 6‐azauridine (4 hour i. v. infusion of 0.2 mg · kg−1 · min−1). Simultaneous infusion of L‐arginine (2.5 μmol · kg−1 · min−1) significantly elevated the blood plasma arginine, ornithine and urea level, however, it did not significantly influence urinary orotate excretion. In normoargininaemia blood plasma turnover of exogenous orotic acid amounted to 4.9 min and 67% of this compound was eliminated through the kidneys. The renal clearance of orotic acid amounted to 21.7ml · min−1 · kg−0.75. Hyperargininaemia elevated blood plasma turnover to 8.2 min, and diminished the renal clearance of this metabolite to 13.7ml · min−1 · kg−0.75. These results indicate that hyperargininaemia and hyperornithinaemia do not change the whole body synthesis of orotic acid in sheep but they can affect renal excretion of this metabolite, particularly at the rate of tubular secretion close to saturation.
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