Adult rats were subjected sequentially to (1) administration of colloidal carbon, zymosan, or gadolinium; (2) subtotal hepatectomy, bilateral nephrectomy, or sham operation; and (3) a 6-hr bout of hypoxia, starting 1 hr or 24 hr after the operation. Control animals received the respective vehicles. The erythropoietin (Ep) activity was assayed in exhypoxic polycythemic mice on the basis of 48-hr per cent RBC(-59) Fe incorporation values. Ep levels in serum of anephric rats primed with either colloidal carbon or zymosan were considerably more elevated than in control animals. This potentiating effect was observed in rats subjected to hypoxia starting either 1 or 24 hr after nephrectomy. On the other hand, gadolinium did not enhance the extrarenal Ep response to hypoxia. It is emphasized that both colloidal carbon and zymosan induced marked hyperplasia of the hepatic and splenic reticuloendothelial system (RES), while gadolinium did not induce this effect. A strict correlation was thus established between potentiation of extrarenal Ep production and hyperplasia of the RES. It is therefore tentatively concluded that the RES is a source of extrarenal Ep. Additionally, since the liver plays a prominent role in extrarenal Ep production, Kupffer cells may represent a major source for Ep in the anephric rat. Finally, it is of interest that both colloidal carbon and zymosan did not potentiate the Ep response to hypoxia in sham-operated or subtotally hepatectomized rats.

Animals↗

PubMed1976

[Participation of the beta-receptor system in the genesis of the carotid aortic baroreceptor reflex in the dog (author's transl)].

The effects of propranolol, given by close arterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid i.v. administration of norepinephrine were studied in dogs. The integrated areas of vasodilatation were significantly reduced after treatment with propranolol. Thus the conclusion was that adrenergic beta-receptors participate in the reflex vasodilatation, although how they act needs further elucidation.

Animals↗

PubMed1975

Biogenesis of erythropoietin: evidence for pro-erythropoietin in a subcellular fraction of kidney.

The light mitochondrial fraction of hypoxic rodent kidneys, called the renal erythropoietic factor, contains erythropoietin in a pro, or active form. Erythropoietin is released from this inactive form when the renal erythropoietic factor is incubated with normal serum. The biogenesis of erythropoietin possibly involves a system in kidney reminiscent of the proinsulin-insulin system in pancreas.

Animals↗

PubMed1975

Erythropoietin production by the liver in fetal-neonatal life.

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Animals↗

PubMed1975

Pure red cell aplasia: studies on an IgG serum inhibitor neutralizing erythropoietin.

A new type of IgG serum inhibitor in adult pure red cell aplasia (PRCA) has been investigated. This inhibitor is directed against circulating erythropoietin (Ep) (PRCA type B), rather than the erythroid marrow (PRCA type A). Thus, the IgG inhibitor, after interaction with Ep in solution, is precipitated together with Ep by addition of goat anti-human gamma-globulins. Pre-therapy PRCA serum, although apparently devoid of Ep, shows considerable Ep activity following acidification and boiling. The inhibitor is absent from post-therapy serum, while Ep levels are elevated. An experimental model for PRCA type B has been established in normal mice after prolonged administration of pre-remission serum IgG.

Aged↗

PubMed1975

Studies on the nature of the vasodilator fibers running in the lumbar sympathetic chain of the dog.

These experiments were performed to further elucidate the nature of the vasodilator fibers running in the sympathetic chain in the dog. The electrostimulation of the lumbar sympathetic trunk caused vasoconstriction in the perfused hind limb which inverted to vasodilatation after guanethidine was administered. This vasodilator response is mediated by cholinergic fibers since it was completely abolished by atropine. The observation, furthermore, that hexamethonium completely nullified both vasodilator and vasoconstrictor responses to the electrostimulation of the sympathetic chain indicates that both vasoconstrictor and vasodilator fibers, which are activated during the stimulation of the sympathetic chain, are preganglionic in nature.

Animals↗

PubMed1975

Studies on the hemodynamic changes induced by electrical stimulation of the vagosympathetic trunks in the dog.

The effects of electrostimulation of the cephalic endings of the vago-sympathetic trunks on the systemic and perfusion pressure of the hind limb of the dog depend upon frequency, intensity and duration of the stimulus. The electrostimulation performed with stimuli of high frequency, low intensity and moderately long duration (rectangular waves of 1.5 V, 0.7 msec, 100 Hz) consistently elicited systemic hypertension and vasoconstriction. This response was completely abolished by pretreatment with guanethidine or hexamethonium. On the other hand, electrostimulation with stimuli of low frequency, high intensity and long duration (5 V, 1 msec, 10 Hz) produced systemic hypotension and vasodilatation in the perfused hind limb. These effects were completely blocked by atropine or hexamethonium, while guanethidine was unable to induce any modification. These findings suggest that electrostimulation of vagosympathetic trunks can evoke different hemodynamic responses depending upon the characteristics of the stimulus. The occurrence of a vasodilatation specifically blocked by atropine demonstrates that a purely cholinergic mechanism underlies such a reflex response.

Animals↗

PubMed1975

Reduction of circulating insulin levels during the infusion of different prostaglandins in the rat.

The intravenous infusion of prostaglandin (PG) E1, E2, and A1 into normal rats at a dose of 2 mug/min significantly lowered plasma insulin levels with a tendency to recovery in the post infusion period. Whereas PGA1 infusion resulted in a moderate but significant hypoglycaemia, the administration of E-series PGs always produced a hyperglycaemic effect. The interference of PGE1 on insulin response to classical insulinogogues (glucagon, aminophylline, and tolbutamide) was also investigated. The results of these experiments demonstrate that PGE1 exerts an inhibitory action on insulin response to all insulin releasing agents investigated. As regards the haemodynamic effects of PGs, PGE1 and PGE2 lowered the arterial blood pressure by about 20 percent, while PGA1 was almost completely ineffective. On the other hand, the lowering effect of PGE1 on circulating insulin levels remained unchanged in rats treated with reserpine. These findings thus rule out a sympathetic over-activity secondary to the lowered arterial blood pressure as the mechanism of action of PGE1. A possible direct interference with the adrenergic receptor system of the pancreatic islets was also ruled out since the inhibitory effect of PGE1 was not overcome by phentolamine pre-treatment.

Aminophylline↗

PubMed1975

Effects of theophylline on glucose kinetics in normal and sympathectomized rats.

The influence of intraperitoneal administration of aminophylline on the rate of hepatic glucose production and peripheral uptake (Ra and Rd) was studied in normal and in adrenodemedullated and reserpinized rats by using the primed constant infusion of Glucose-2-3H. In normal rats, the dose of 100 mg. per kilogram of aminophylline produced a marked increase of Ra and Rd. Since Ra rose more rapidly than Rd did initially, hyperglycemia developed. Thereafter, glucose production and uptake increased to nearly the same extent, and a new steady state was reached at plasma glucose levels almost twice those of the baseline. Smaller and transient modifications were observed after the administration of 20 mg. per kilogram of aminophylline. With the higher dose, insulin levels markedly rose (reaching a tenfold peak above the basal value) while minor increments were observed with the lower dose. In a group of normal rats which were given glucose (10 mg. per kilogram per minute) in order to achieve a degree of hyperglycemia comparable to that brought about by the higher dose of aminophylline, an almost identical enhancement of glucose uptake was recorded. However, insulin levels were much higher in aminophylline-treated rats as compared to normal rats. From these finding it was concluded that aminophylline induces resistance to insulin effect. When aminophylline was injected into demedullated rats pretreated with reserpine, at the dose of 100 mg. per kilogram, a marked enhancement of Ra, and consequently of glycemia, was recorded initially; later, severe hypoglycemia developed depending on both a progressive exhaustion of hepatic glucose production and a marked increase of glucose utilization. Insulin levels dramatically increased in these experiments. These results suggest that aminophylline directly increases glucose production by the liver and insulin secretion. The simultaneous activation of the sympathetic system blunts the insulin response and counteracts the restraining effect of insulin on the liver and the stimulatory effect of insulin on overall glucose uptake as well.

Adrenal Medulla↗

PubMed1975

Pure red cell aplasia (PRCA): Response of three patients of cyclophosphamide and/or antilymphocyte globulin (ALG) and demonstration of two types of serum IgG inhibitors to erythropoiesis.

Three cases of adult pure red cell aplasia (PRCA) ARE REPORTED. All patients proved refractory to various combinations of androgens and corticosteroids. The first case, harboring a thymoma, showed a complete clinical remission following cyclophosphamide therapy. The second and third responded similarly to either a combined cyclophosphamide + antilymphocyte globulin (ALG) treatment or to ALG administration preceded by a small dosage of cyclophosphamide, which had proved ineffective when administered alone. Serum IgG inhibitors to erythropoiesis were demonstrated in all cases by means of in vivo and/or in vitro techniques. The inhibitor(s), although directed against the erythroid marrow in both the first and third patients (PRCA type A), apparently functioned as an antibody to circulating erythropoientin (Ep) in the second case (PRCA type B). The inhibitor(s) was always absent in postremission samples. Additionally, experimental models for both types of human PRCA were established in normal rodents. The present studies support the contention that adult PRCA is an autoimmune disease. The therapeutic role of cytotoxic-immunodepressive agents in PRCA patients is confirmed. It is emphasized that ALG may represent an additional therapeutic tool in cases resistant to cyclophosphamide and/or steroids. In addition, cyclophosphamide proved effective in a patient harboring a thymoma not amenable to surgery. Finally, it is postulated that IgG serum autoantibodies, directed against either an early erythroid precursor (PRCA type A) or, more rarely, circulating Ep (PRCA type B), play a major role in the pathogenesis of the disease.

Aged↗

PubMed1975