Increased Plasma Uric Acid Research Articles

Nitrogen excretion in “maximally-fed” crocodilians

1. 1. Alligators fed ab lib 5 days a week excreted the same amount of uric acid/day, but much more ammonia/day, than those fed a single meal after a long fast. 2. 2. Plasma levels of ammonia (and uric acid) precursors were the same in the two groups. 3. 3. Uric acid clearance rates varied directly with rates of ammonia excretion (and with urine vol), so, with a low ammonia excretion in the single-meal group, there was a decreased uric acid clearance (and probably an increased uric acid synthesis), with a consequent increase in plasma uric acid not seen in the maximally-fed group.

Adrenal epinephrine in hyperuricemia induced by hypothalamic stimulation of the rat.

Peripheral neurological mechanisms involved in hyperuricemia following ventromedial hypothalamic electrical stimulation was studied in the conscious rat. The intensity of 0.2 mA was near the maximum intensity of stimulation current producing a linear increase in plasma uric acid throughout the 15-min period of stimulation, as well as a subsequent rise and fall of plasma allantoin. Bilateral adrenal demedullation abolished the stimulation-induced hyperuricemia and markedly impaired the accompanying rise of allantoin. Prior treatment of the animal with hexamethonium significantly inhibited the uric acid increase, but did not reduce the allantoin elevation so markedly. Moreover, propranolol eliminated both responses of these plasma purine metabolites, whereas phentolamine greatly increased the response. It is concluded therefore that the hypothalamic stimulation-induced rise of plasma uric acid is the result of acceleration of epinephrine release from the adrenal medulla and that, whereas some unknown extra-adrenal mechanism may be partially involved, the primary part of the accompanying allantoin elevation is explained by the combined effects of the increased uric acid and the hepatic uricase.

Increase of Plasma Uric Acid in Rats Treated with Biogeneamines

Increase of Plasma Uric Acid in Rats Treated with Biogeneamines

STIMULATION BY CATECHOLAMINE OF PURINE CATABOLISM IN RATS AND CHICKENS

The effect of catecholamine in vivo was studied on purine catabolism in rats and chickens. Catecholamine, administered intraperitoneally in a high dose, markedly increased plasma uric acid and allantoin in rats, and an increase was also observed with intravenous infusion of a lower dose of catecholamine. The effects of catecholamine were characterized by inhibition with alpha and beta adrenoceptor antagonists. Regarding the mechanism of this catecholamine action on purine catabolism, it was shown that catecholamine stimulated degradation of tissue ATP into the end-product. Plasma allantoin, the final purine catabolite in rats, elicited by catecholamine could be maintained under conditions of renal failure, although the action of catecholamine in intact rat was short lasting. The effect of catecholamine was potentiated and/or prolonged by angiotensin-II and aminophylline, and a hyperuricemic state could be induced by catecholamine treatment in chickens. In addition, increase of plasma purine catabolite by immobilization stress in rats suggested the involvement of endogenous catecholamine. From these experimental results, it is considered that catecholamines probably play a important role in the pathogenesis of hyperuricemia.

Effect of a xanthine oxidase inhibitor on adenine nucleotide degradation in hemorrhagic shock.

Biochemical effects of treatment with a xanthine oxidase inhibitor (allopurinol) were investigated in an experimental hemorrhagic shock procedure. Allopurinol pretreatment abolished the increase in plasma uric acid which occurs in untreated dogs during hemorrhagic hypotension and resulted in a much lesser increase in plasma allantoin. The pancreatic, liver and duodenal adenosine triphosphate (ATP) and total adenine nucleotides of untreated dogs were severely reduced, while those of allopurinol-pretreated dogs were essentially normal 2 h following reinfusion. Pretreatment with allopurinol resulted in a significantly lesser release of the lysosomal enzymes, acid phosphatase and beta-glucuronidase, following reinfusion. When treatment was delayed until after reinfusion, an infusion of hypoxanthine + allpurinol restored normal ATP concentrations. The role of adenine nucleotide breakdown in irreversible shock is discussed.

Origin of plasma uric acid induced by l-epinephrine.

The origin of increased plasma uric acid in l-epinephrine-induced hyperuricemia was studied. It was shown that uric acid is increased by an extra-hepatic process, in particular by reduction in the intestinal adenosine-tri-phosphate level. Further, from evidence for the existence of plasma xanthine oxidase, it was shown that production of uric acid by an extra-hepatic process is very likely in many mammals, even in man.

The renal excretion of nitrogenous compounds by the duck (Anas platyrhynchos) maintained on freshwater and on hypertonic saline.

ABSTRACT The excretory rates of total nitrogen, uric acid, urea and ammonia by intact birds maintained on fresh water did not differ significantly from the corresponding rates of excretion by birds maintained on saline equivalent to 60 % sea water (284 mM-NaCl, 6·0 mM-KCl). The uric acid excreted by these birds contributed 53·8%, the ammonia 29·2% and the urea 1·5% of the total nitrogen excreted. The three compounds together accounted for 84·5 % of the nitrogen excreted. The glomerular filtration rates (inulin clearance) and the renal plasma flow rates (PAH clearance) did not differ between the freshwater-maintained and the saline-maintained birds. The clearance of uric acid in all groups of birds was equal to the PAH clearance and may be interpreted as a reliable measure of the renal plasma flow rate. The urea:inulin clearance ratios for the individual urine samples from all birds suggested that renal tubular synthesis and secretion of urea may occur. In a second set of experiments uric acid and urea concentrations in the plasma of fed ducks were followed during adaptation to hypertonic saline and during a similar period of dehydration. A sharp in the increase plasma uric acid concentration was generally observed in all groups of birds after feeding and the concentration then gradually declined to the prefeeding level. The plasma urea concentrations of birds given saline equivalent to 60% sea water equilibrated, after the first 24 hr., at about twice the concentration found in the freshwater-maintained birds. In birds maintained on saline equivalent to 100% sea water (470 mM-NaCl; 10 mM-KCl), the plasma urea concentration steadily rose during the first 50 hours and then equilibrated at a level approximately 10 times that observed in freshwater-maintained birds. Withholding all drinking water from birds which had been previously given fresh water resulted in a rise in the plasma urea concentration during the first 50 hr. similar to that observed in the birds maintained on saline equivalent to 100% sea water. But the plasma urea concentration of these birds, in contrast to that of saline-maintained birds, continued to rise throughout the remainder of the experimental period.

Renal function in gout: II. Effect of uric acid loading on renal excretion of uric acid

Thirteen non-gouty and twelve gouty men to whose regular diet was added 4 gm. of ribonucleic acid (RNA) daily, developed increases in plasma uric acid, urinary excretion of uric acid and derived parameters, without significant differences in the mean increments in non-gouty and gouty subjects. Ten non-gouty and seventeen gouty men were given intravenous injections of 1.1 to 2.5 gm. uric acid to impose even greater demands upon the tubular mechanisms for transfer of uric acid, and again the mean increments in the urinary excretion of uric acid and uric acid clearance in non-gouty and gouty subjects were indistinguishable. Pyrazinoic acid, a potent inhibitor of tubular secretion of uric acid, was found to suppress the urinary elimination of rapidly infused uric acid in gouty and non-gouty subjects alike.The data indicate that gouty subjects can excrete large extraneous loads of uric acid with as much facility as normal man, and support the view that this obtains also for the usually smaller and more slowly delivered endogenous uric acid loads natural to gout. The results thus argue against any intrinsic defect, peculiar to gout, in the renal mechanisms for excretion of uric acid.Briefly reviewed is the evidence that tubular secretion of uric acid occurs in non-gouty and gouty man, indeed that virtually all the uric acid appearing in the urine ordinarily derives from tubular secretion, hence virtually all the filtered uric acid ordinarily must be reabsorbed. It is pointed out that in this version of the filtration-reabsorption-secretion hypothesis there need be no simple relationship between the filtered and excreted uric acid, a dissociation found in gout that has been interpreted by others as indicating a primary tubular defect in transfer of uric acid. The implications of the filtration-reabsorption-secretion hypothesis in respect to other aspects of the renal regulation of uric acid are discussed in relation to excretion of uric acid in normal and gouty man under natural and artificial conditions of uric acid loading.The present study, limited to over-all clearances, gives no information as to the precise mechanisms or quantitative aspects of tubular secretion of uric acid in normal or gouty man, nor does it explain just how renal excretion of large and rapidly imposed uric acid loads is regulated.