The effects of reducing dietary nitrogen and of increasing sodium chloride intake on urea excretion and reabsorption and on urine osmolality in sheep.

Renal responses to reducing dietary nitrogen were studied in four ewes during intravenous infusion of arginine vasopressin. The fall in urea excretion and in plasma urea concentration was accompanied by significant reduction in GFR and in urine osmolality. The fraction of filtered urea reabsorbed increased despite reduction in the urea U/P concentration ratio and this increase was sustained when the urea U/P ratio was further reduced at higher urine flows observed when the drinking water was replaced with saline. This procedure also sustained the RPF which in the absence of additional salt was significantly reduced on the low protein diet. It is suggested that the fall in GFR and the increase in the fraction of filtered urea reabsorbsed may contribute to nitrogen economy and that the increase in fractional reabsorption and the reduction in urine osmolality on the low protein diet provided evidence of active reabsorption of urea by renal tubules.     

Effects of angiotensin on proximal tubular reabsorption

Effects of angiotensin II on rat, rabbit, and bovine proximal tubular reabsorption have been demonstrated with a variety of techniques, including in vivo microperfusion, free-flow micropuncture of surface and juxtamedullary nephrons, perfusion of isolated tubules in vitro, and cell culture. Blockade of endogenous angiotensin production in vivo with converting-enzyme inhibition, or of receptors with saralasin, consistently inhibits proximal reabsorption of fluid in both superficial and juxtamedullary proximal tubules. Angiotensin effects on the proximal tubule are not neurally mediated, for they persist in denervated kidneys and are seen in nerve-free isolated tubules. Physiological concentrations of angiotensin (10(-11)-10(-9) M) stimulate electroneutral sodium transport from the basolateral membrane, whereas pharmacological doses (10(-7) M and above) inhibit reabsorption. The stimulatory effects appear to be receptor mediated. In addition to these direct effects of angiotensin on the proximal tubule epithelium, endogenous angiotensin may also alter peritubular physical forces to further enhance proximal reabsorption. These effects of angiotensin may represent an important homeostatic mechanism during states of extracellular fluid volume depletion.     

Effect of dietary protein intake on plasma leucine flux, protein synthesis, and degradation in sheep

Combined experiments of an isotope dilution method of [1-(13)C]leucine with open circuit calorimetry and a nitrogen (N) balance test were applied to determine the effect of dietary crude protein (CP) intake on plasma leucine flux and protein synthesis and degradation in four sheep. The experiment was conducted in a 3 x 4 Latin rectangle design of three 3-week periods. Dietary CP intake was 5.6, 7.7, and 10.8 g/(kg(0.75) x d). Metabolizable energy intake was 120% of requirement for all dietary treatments. [1-(13)C]Leucine was intravenously infused for 8 h and blood and breath samples were collected during the latter 2-h period of infusion. Isotopic enrichments of plasma [1-(13)C]leucine, alpha-[1-(13)C]ketoisocaproic acid, and exhaled (13)CO(2) were determined. For the N balance test, N digestibility, N excretion in urine, and protein balance (N x 6.25) increased with increasing dietary CP intake. Rates of plasma leucine turnover, protein synthesis, and degradation changed toward reduction with increased dietary CP intake. It is likely that in sheep, high CP intake enhances protein deposition with reduced protein degradation rather than increased protein synthesis.     

Coordination of kidney filtration and tubular reabsorption: considerations on the regulation of metabolic demand for tubular reabsorption

Kidney blood flow is highly regulated by a combination of myogenic autoregulation, multiple neurohormonal systems and the tubuloglomerular feedback system, the later of which specifically relates tubular reabsorption to the filtered load. Oxygen and substrate requirements of the kidney are dictated by both supply of oxygen and substrates and metabolic demands of the kidney. The tubuloglomerular feedback system utilizes mediators which are intimately linked to cellular metabolism, ATP and adenosine. This system based upon communication transfer between the macular densa and the afferent arteriole stabilizes kidney function and is not static but temporally adapts or resets to new external physiologic conditions. Such temporal adaptation occurs via modulators such as nitric oxide (NO), primarily derived from NOS-1, angiotensin II and COX-2 products. These hormonal influences also exert capacities to modulate cellular demands for oxygen, particularly NO which decreases oxygen consumption via multiple mechanisms. The several mechanisms whereby NO and other hormonal systems and transporter activity can regulate and produce changes in kidney metabolic demands are discussed. Modulators which influence temporal adaptation and resetting of TGF are also significant contributors to the regulation of cellular oxygen consumption in the kidney. These systems may act in concert to preserve the coordination of filtered load and tubular reabsorption and the metabolic demands of kidney function, thereby determining the ischemic threshold for kidney function.     

The renal response of sheep to a low dietary nitrogen intake

Renal functions were tested in sheep fed on a low nitrogen diet (LN sheep), with a daily N intake of 4.7 g (gross energy 17.76 . 10(6) J). Sheep given a high nitrogen diet (HN sheep) with 21.2 g N (24.12 . 10(6) J) acted as the control. The functions of the left kidney were measured in anaesthetized animals by the standard clearance technique. A comparison of HN and LN sheep showed that a low nitrogen intake led to a drop in the plasma urea level (from 5.91 +/- 0.35 to 2.87 +/- 0.36 mmol.1-1, (P less than 0.001), the glomerular filtration rate (GFR, from 36.6 +/- 3.6 to 20.7 +/- 2.4 ml.min-1, P less than 0.005), amount of urea excreted (from 106.7 +/- 18.1 to 15.7 +/- 3.3 mumol.min-1, P less than 0.001), fractional urea excretion (from 51.0 +/- 3.0 to 24.6 +/- 3.1 %, P less than 0.001) and the absolute tubular reabsorption of urea (Reaburea/GFR (from 3.06 +/- 0.27 to 2.12 +/- 0.28 mumol.ml-1, P less than 0.05), without a significant change in the effective renal plasma flow (182.6 +/- 20.0 and 138.5 +/- 21.0 ml.min-1, non-significant - N.S.) and in sodium and potassium excretory function. Free water clearance rose in LN sheep (from -0.53 +/- 0.11 to -0.19 +/- 0.06 ml.min-1, P less than 0.05) owing to inhibited urea excretion. A regression analysis of the relationship of the tubular reabsorption of urea to the amount of filtered urea (both normalized to the GFR) showed that the urea transport capacity of the tubules of LN sheep was significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of dietary protein on the capacity of urea synthesis in rats

The in vivo capacity of urea nitrogen synthesis (CUNS) during alanine stimulation was measured within the blood amino acid concentration interval 7.3-11.6 mmol/l, where urea synthesis is at maximum and independent of substrate concentration. Three groups of rats were fed for 14 days, either a low protein diet (8%), a normal diet (17%), or a high protein diet (53%). Diet protein modified both CUNS and plasma glucagon concentration. CUNS was 5.86 +/- 2.93, 7.43 +/- 2.16, and 19.31 +/- 4.32 mumol/(min.100 g BW) (mean +/- SD, N = 6), respectively. The corresponding plasma glucagon concentrations after alanine stimulation were 222 +/- 400, 633 +/- 229, and 1700 +/- 627 ng/l, respectively. The in vivo kinetics of urea production is regulated by dietary protein, possibly via glucagon. This implies that the liver plays an active part in adaptation of whole body nitrogen homeostasis to dietary changes.     

Effect of ghrelin in dry matter intake and energy metabolism in prepartum sheep: a preliminary study

The objective of this study was to determine the effect of ghrelin on dry matter intake and energy metabolites in ewes during the last 10d of gestation. Ewes were randomly assigned to either a treatment (n=6) or a control group (n=6). One hour after feeding (08:00 and 16:00), ewes in the treated group were given ovine ghrelin (3 microg/kg, i.m.) and the control group received an equivalent volume of saline. Treatments were continued until lambing. Daily blood samples were taken starting at assignment. The principal findings were that: (1) ewes treated with ghrelin had a higher dry matter intake only on the first day of treatment; (2) treated ewes had lower serum concentrations of non-esterified fatty acids and insulin but higher serum concentrations of growth hormone; (3) serum concentrations of beta-hydroxy butyrate and cortisol were not different between treated and non-treated ewes. In conclusion, treatment with ghrelin affected dry matter intake and energy metabolites of pre-partum ewes during the last 10 d of pregnancy.     

Effect of dietary hempseed intake on cardiac ischemia-reperfusion injury

Polyunsaturated fatty acids (PUFAs) have significant, cardioprotective effects against ischemia. Hempseed contains a high proportion of the PUFAs linoleic acid (LA) and alpha-linolenic acid (ALA), which may have opposing effects on postischemic heart performance. There are no reported data concerning the cardiovascular effects of dietary hempseed intake. A group of 40 male Sprague-Dawley rats were distributed evenly into four groups that were fed for 12 wk a normal rat chow supplemented with hempseed (5% and 10%), palm oil (1%), or a 10% partially delipidated hempseed that served as a control. Plasma ALA and gamma-linolenic acid levels were significantly elevated in the rats that were fed a 5% or 10% hempseed-supplemented diet, but in heart tissue only ALA levels were significantly elevated in the rats fed these diets compared with control. After the dietary interventions were completed, postischemic heart performance was evaluated by measuring developed tension, resting tension, the rates of tension development and relaxation, and the number of extrasystoles. Hearts from rats fed a hempseed-supplemented diet exhibited significantly better postischemic recovery of maximal contractile function and enhanced rates of tension development and relaxation during reperfusion than hearts from the other groups. These hearts, however, were not protected from the occurrence of extrasystoles, nor were the increases in resting tension altered during ischemia or reperfusion as a function of any dietary intervention. Our data demonstrate that dietary hempseed can provide significant cardioprotective effects during postischemic reperfusion. This appears to be due to its highly enriched PUFA content.