Elevated urinary excretion of orotic acid in sheep caused by intraruminal infusion of sodium propionate.

1. The effect of sodium propionate on urinary excretion of orotic acid was investigated. 2. Solutions containing sodium propionate or NaCl, 750 mM/day each, were continuously infused into the rumen for 10 days. 3. During NaCl infusion, an urinary orotic acid excretion of 290 +/- 80 micrograms/day was noted. The intraruminal infusion of sodium propionate raised the concentration of propionic acid in the rumen fluid from 14.0 +/- 0.9 to 26.9 +/- 1.9 mM. 4. During this experimental period the excretion of orotic acid via urine significantly increased to 492 +/- 30 micrograms/day. Parameters of nitrogen balance were not altered by propionate. 5. It is suggested that the site of propionate action in intact sheep is in the pyrimidine synthesis pathway.     

Utilisation of fish oil in ruminants: I. Fish oil metabolism in sheep

Five sheep with rumen and abomasal cannulae were offered three diets sequentially in the order: control (C) pellets (lucerne hay-oat grain: 60/40, w/w), control plus unprotected tuna oil (UTO pellets), and control plus tuna oil protected (casein-formaldehyde matrix) against ruminal biohydrogenation (PTO pellets). In supplemented diets, tuna oil constituted 3% (w/w) of total dry matter (DM), and each supplement was fed for 12 days, with 9 days allowed between the two fish oil feeding periods to minimise carry-over effects. Daily DM intake was 785±38 g/head during the control period. It was significantly reduced by UTO feeding (6.2%, P<0.05) but not PTO feeding. The level of EPA in the abomasum during PTO feeding was double that measured during UTO feeding (1.30 versus 0.61% of FA, P<0.05). The level of DHA in the abomasum did not significantly differ between UTO and PTO feeding periods. Both tuna oil supplements significantly increased the levels of 18:1 trans and that of a fatty acid derivative identified as 10-hydroxystearic acid (10-HSA) in both the rumen and abomsum. Tuna oil supplementation also altered the fatty acid composition of plasma lipid fractions and 10-HSA was solely incorporated into plasma free fatty acids. This study indicates that substantial protection of tuna oil against ruminal hydrogenation inhibited reduced feed intake, but increased the proportion of 18:1 trans isomer and fatty acids derivatives (10-HSA), which indicate interference with metabolism in the rumen.     

Sulfur and methionine metabolism in sheep. I. First approximations of sulfur pools in and sulfur flows from the reticulo-rumen.

Sulfur pools in the rumen and sulfur flows from the rumen were investigated in two experiments with sheep on a diet containing equal parts of oaten and lucerne chaffs. The diet was fed at two levels, either chopped or pelleted, and with intraruminal DL-methionine supplements. Ruminal fluid volumes and fluid flows to the omasum were measured. None of the treatments influenced ruminal fluid volume. Fluid flow to the omasum, however, was increased by increasing dry matter intake (DMI), and was further enhanced by feeding chaffed hay rather than the same materials ground and pelleted; the DL-methionine supplement had no effect. First approximation of the ruminal sulfur pools and of sulfur flows to the omasum were derived from the concentration of sulfur in true digesta and the ruminal fluid volume or fluid flow. Increasing DMI from 500 to 1000 g/day resulted in larger ruminal pools of total (1096 v. 792 mg), neutral (1016 v. 731 mg) and protein (479 v. 419 mg) sulfur, but the reducible sulfur pools were not affected by the level of DMI. Infusions of DL-methionine increased the ruminal sulfide sulfur pool irrespective of level of DMI. The first approximation of total sulfur flow was increased by 1660 mg/day at the higher level of DMI, due mainly to increases of 710 mg S/day as protein sulfur and 859 mg S/day as non-protein neutral sulfur. Flows of inorganic sulfate and ester sulfate sulfur, although small in comparison with organic sulfur flows, increased with level of DMI. Sulfide sulfur flows were also increased at the higher level of DMI, and were almost doubled by intraruminal infusions of DL-methionine.     

The rapid adjustment of renal sodium excretion to changes in dietary sodium intake in sheep

The rapidity with which the kidney alters sodium excretion (ENa) in response to changes in dietary Na was studied in Merino sheep by analyzing hourly ENa for three control days, and then for three days after a change in Na intake. On a control diet of 117 mmol Na, sheep had a pre-feeding ENa of 3.5 mmol/hr., a striking post-feeding natriuresis that began 2 hours after feeding (less than 0.01), peaked at 4 hrs. and then declined to pre-feeding levels 7 hrs. after feeding. When in balance on a high Na diet the feeding of a low Na meal resulted in marked depression of ENa within 4 hours after feeding. On a low Na diet, a 100 mmol Na meal resulted in an increase in ENa within 4 hours but a 50 mmol Na meal did not. Thus, the sensitivity of post-feeding natriuresis is between 50 and 100 mmols Na. As post feeding natriuresis is a naturally occurring physiological event it should provide a useful paradigm for the investigation of mechanisms controlling Na balance.     

Sulfur and methionine metabolism in sheep. II. Quantitative estimates of sulfur metabolism in the sheep's stomach.

The metabolism of dietary and supplemental DL-methionine sulfur in the stomach of sheep was studied in two experiments. In both experiments sheep were fed a 50 : 50 oaten chaff: lucerne chaff ration at two levels of intake, and some animals received intraruminal infusions of DL-methionine. In experiment 2 increasing dry matter intake (DMI) increased first approximations of total, neutral, protein and reducible sulfur flows and also sulfide sulfur flow from the reticulo-rumen. Increased DMI (from 500 to 1000 g/day) also resulted in greater true flows of total (2207 v. 1104 mg/day), neutral (1867 v. 1043 mg/day) and protein (893 v. 482 mg/day) sulfur at the duodenum. Two flow diagrams of sulfur metabolism in the compartments of the ruminant stomach were developed from the data of experiment 2. Fluid flows of sulfur in experiment 1 were used to supplement the data of experiment 2 in developing the balance models. The two models represent the extremes of dietary and supplemental sulfur metabolism in the sheep's stomach under the conditions of experiment 2, and they are discussed in relation to previous research on sulfur metabolism in the stomach.     

Effect of lactate and beta-hydroxybutyrate infusions on brain metabolism in the fetal sheep

Brain uptake of substrates other than glucose has been demonstrated in neonatal but not fetal animals in vivo. This study was undertaken to investigate the ability of the fetal sheep brain to use potential alternative substrates when they were provided in increased amounts. Brain substrate uptake was measured in chronically catheterised fetal sheep during 2-h infusions of neutralised lactate (n = 12) or beta-hydroxybutyrate (n = 12). Despite large increases in fetal arterial lactate and beta-hydroxybutyrate during the respective infusions, no significant uptake of either substrate was demonstrated. However during both types of infusion, the brain arterio-venous difference for glucose decreased 30% (P less than 0.05). Since the brain arterio-venous difference for oxygen was unchanged, and blood flow to the cerebral hemispheres (measured in 11 studies) was also unchanged, the infusions appeared to cause a true decrease in brain glucose uptake. This decrease paralleled the rise in lactate concentration during lactate infusions, and the rise in lactate and butyrate concentrations during the butyrate infusions. Both substrates have metabolic actions that may inhibit brain glucose uptake. We speculate that the deleterious effects of high lactate and ketone states in the perinatal period may in part be due to inhibition of brain glucose uptake.     

The absorption, metabolism and excretion of dimethyl sulfoxide by rhesus monkeys

The absorption and excretion of dimethyl sulfoxide (DMSO) were studied in Rhesus monkeys (Macaca mulatta) given daily oral doses of 3 gms DMSO/kg B.W. for 14 days. DMSO and its major metabolite, dimethyl sulfone (DMSO2), were measured in serum, urine and feces by gas-liquid chromatography. DMSO was absorbed rapidly, reached a steady state blood level after 1 day and then was cleared from blood within 72 hrs after ending treatment. Serum DMSO declined in a linear fashion on semilogarithmic coordinates as described by second order kinetics. It had a half-life of 16 hrs. DMSO2 appeared in blood within 2 hrs and reached a steady state concentration after 4 days of treatment. DMSO2 was cleared from blood about 120 hrs after DMSO administration was stopped. Its half-life in blood was calculated to be 38 hrs. Urinary excretion of unmetabolized DMSO and DMSO2 accounted for about 60% and 16%, respectively, of the total ingested dose. Neither DMSO nor DMSO2 was detected in fecal samples. However, when added to fecal samples, DMSO was degraded rapidly. Although dimethyl sulfide (DMS) was not measured, some DMSO was metabolized to this compound because of the particular sweetness of breath of the monkeys. We conclude that the absorption of DMSO by monkeys is similar to that for humans, but that its conversion to DMSO2 and urinary elimination are more rapid in monkeys.