Einfluss von synthetischem Bradykinin und Kallidin auf die Chemoreceptoren der Gefässe der hinteren Extremität der Katze

Summary The hindlimb of cat was separated from the body, the sciatic nerve remaining intact, The separated hindlimb was perfused through the femoral artery with tyrode solution. Synthetic bradykinin and kallidin injected into the femoral artery elicit vasoconstriction in the hindlimb, reflex on the systemic blood pressure, and stimulation of respiration. We assumed the cause of this reflex to be general sympathetic excitation through stimulation of chemoreceptor cells in the blood vessels of the hindlimb of the cat.     

Zur Spezifität des durch Bradykinin,Kallidin und Met-Kallidin ausgelösten Blutdruckreflexes an der Katze

Summary Synthetic kinins (bradykinin, kallidin and met-kallidin) administered via the femoral artery in the isolated hindlimb of the cat elicits vasoconstriction, a reflex on the systemic blood pressure, a stimulation of respiration, and contraction of nictitating membrane. Acetylcholine elicits these reflex reactions in the body too. Atropine blocks this reflex, but not the reactions of kinins. Phenylbutazone administered via the femoral artery blocks the reflex reactions of acetylcholine and kinins as well as the vasoconstriction of histamine and the kinins in the isolated hindlimb. Phenylbutazone elicits by itself a reflex reaction. Of all the synthetic substances, the kinins are the most specific drugs inducing reflex reactions.     

The influence of aromatic amines and folate on acid production byEscherichia coli

Summary Folinic acid, adrenaline and noradrenaline, substances known to stimulate oxygen consumption byE. coli, are shown in this experiment to do so by different mechanisms. This work demonstrates stimulation of acid production by folinic acid and inhibition by adrenaline and noradrenaline.Acknowledgment. The authors thank Mr C.A. James for his technical assistance with this work.     

Gefässkonstriktion durch synthetisches Bradykinin und ihre pharmakologische Beeinflussbarkeit

Summary The divided hindlimb of the cat was perfused through the femoral artery with tyrode solution. Synthetic bradykinin administered via the artery elicits a vasoconstriction,- and-sympathicolytics decrease the vasoconstriction, cocain and guanethedin emphasize it, whilst iproniacid and reserpin have no influence on it. It is assumed that bradykinin acts directly on adrenergic structures of the vessels of the hindlimb of the cat.     

Influence of hypoxia on contractility and calcium uptake in rabbit aorta

Summary The influence of hypoxia on noradrenaline (NA)-induced contractions and⁴⁵Ca uptake has been studied on isolated rabbit aortae. Hypoxia significantly decreased the contractility of aortic strips. NA stimulation resulted in increased or decreased⁴⁵Ca uptake by normoxic or hypoxic specimens, respectively. Relating⁴⁵Ca movement with mechanical activity, the results suggest that decrease in Ca⁺⁺ uptake may be mechanism for hypoxic relaxation of aortic smooth muscle.The author acknowledges facilities at the Wellcome Surgical Research Institute, University of Glasgow, U.K. Much of this work was in collaboration with Drs Sheila Jennett and J.D. Pickard.     

Further evidence for the existence of a bottleneck in the metabolism of Saccharomyces cerevisiae

The growth physiology of Saccharomyces cerevisiae strains H1022 and Whi2+ has been studied in aerobic batch and continuous (chemostat) cultures. Results from the measurement of biomass and medium components (off-line) together with oxygen, carbon dioxide and heat measurements (on-line) have been used in an attempt to explore the existence of 'overflow' or 'bottleneck' metabolism as opposed to catabolite repression (Crabtree effect) in these strains. Chemostat experiments indicated that specific oxygen uptake rate (qO2) was linearly related to the dilution rate (D) at values below the critical dilution rate (D crit), becoming constant above D crit, which is in agreement with the bottleneck theory. However, batch culture experiments indicated negligible oxygen consumption during the initial glucose growth phase, the culture exhibiting purely anaerobic metabolism. The bottleneck theory would propose that qO2 has a constant (maximum) value under these conditions. The results presented here suggest that while the bottleneck theory can be adequately used to describe chemostat growth of S. cerevisiae, some other control mechanism must be operating under conditions of high glucose concentrations, such as those initially prevailing in the batch culture experiments.     

Hydrogen peroxide and hydroxyl radical involvement in the activation of caspase-3 in chemically induced apoptosis of HL-60 cells

Apoptosis of HL-60 cells induced by actinomycin D, H7, or daunorubicin was shown to involve the activation of caspase-3-like protease, 2 h after the addition of these drugs, based on microassay of enzyme activity by high-performance liquid chromatography. Catalase and a spin trap, N-t-butyl--phenylnitrone, which effectively inhibited the apoptosis induced by these drugs, also inhibited the activation of caspase-3-like protease. These results suggest that hydrogen peroxide and the hydroxyl radical are common mediators of caspase-3 activation caused by these chemicals, with apparently different functional mechanisms. Based on mitochondrial activity determined by oxygen consumption, complexes I, II, and IV were inhibited by actinomycin D. H7 inhibited complexes I and IV, 1 and 1.5 h respectively, after the addition of the drug to HL-60 cells. Daunorubicin inhibited complex IV, 1.5 h after the addition of the drug to HL-60 cells. Inhibition of complex IV by actinomycin D, H7, and daunorubicin were almost fully restored by the addition of cytochrome c. The release to the cytosol of cytochrome c by these drugs was also demonstrated by Western blot analysis. Addition of catalase inhibited the depression of complex IV activity induced by actinomycin D and H7. These observations indicate a direct relationship between hydrogen peroxide and the release of cytochrome c during apoptosis caused by actinomycin D, H7, and daunorubicin. Received 24 November 2000; received after revision 2 January 2001; accepted 30 January 2001     

The effect of camphor on mitochondrial respiration

Summary Camphor at <8 moles/mg protein reduced the rate of oxygen consumption by rat liver mitochondria. The effect occurs only with NAD⁺-linked substrates. Succinate linked respiration was inhibited but this appears to be caused by some conversion of succinate to malate. At higher levels, camphor increases oxygen consumption with succinate substrate, by uncoupling at site II.Acknowledgment. D.F.G.-C. is grateful to the New Zealand Cancer Society (Wellington Branch), for financial support. We thank Mrs E. Dye for technical assistance and Dr W. Jordan for valuable discussions.     

Inflammation and repeated infections in CGD: two sides of a coin

Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals. It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells (neutrophils, eosinophils, monocytes, and macrophages). This “respiratory burst” involves the catalytic conversion of molecular oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients.     

Responses of monkey, rabbit and dog internal carotid arteries to atrial natriuretic factor

Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10-30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

Responses of monkey,rabbit and dog internal carotid arteries to atrial natriuretic factor

Summary Effects of atrial natriuretic factor (ANF) on monkey, rabbit and dog internal carotid arteries were investigated. ANF caused a concentration-dependent relaxation in arterial strips submaximally precontracted with noradrenaline, 5-hydroxytryptamine, or high-potassium solution (10–30 mM). The response was greatest in the monkey arteries and least in the dog arteries. These results suggest that there is a marked species difference in the ANF-induced relaxation of the internal carotid arteries.     

The effect of L-dopa on pupillary diameter in mice

Summary Injection of L-dopa in mice produces dose-dependent mydriasis. Pre-treatment with peripheral dopa-decarboxylase inhibitors (carbidopa and benserazide) or with an alpha-adrenergic blocking agent (phentolamine) abolishes the pupillary dilation caused by L-dopa. Pretreatment with fusaric acid, an inhibitor of dopamine-beta-hydroxylase, also antagonizes the mydriatic effect of L-dopa. Thus, our results suggest that the mydriasis produced in mice following the injection of L-dopa is caused by its peripheral conversion to noradrenaline, which stimulates alpha-adrenergic receptors in the dilator iridis. There was no evidence that stimulation of specific dopaminergic receptors was involved.We are grateful to N. Rothschild, Head of Laboratory Animal Department, Sackler School of Medicine, for his help.     

The influence of 6-OHDA on hypothermia produced by intrahypothalamically-injected carbachol in the pigeon

Summary The involvement of the noradrenergic system in hypothermia induced by intrahypothalamically-injected carbachol (CCh) was studied by depleting hypothalamic noradrenaline (NA) with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) and repeating the CCh injections after 6-OHDA treatment. The results suggest that noradrenergic neurons may be involved in hypothermia produced by CCh in the pigeon.     

Relation entre l'activité de la glande thyroÏde et la consommation d'oxygène chez les Téléostéens,Cichlidés

Summary The study of the relationship between the activity of the thyroid of Cichlid fishes and oxygen consumption has given the following results: The stimulation by thyroxine causes a significant increase of oxygen consumption (+35%) after a long treatment. This increase is not immediate; a latent period is observed till the gland is in repose. The antithyroid rapidly decreases the oxygen consumption (–24%). But this chemical blocking is not stable.     

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat

Administration of glucagon to rats at 25 degrees C had no effect upon their VO2, while administration of noradrenaline or noradrenaline plus glucagon raised the VO2. At 5 degrees C, noradrenaline had no effect upon the cold-enhanced VO2, while glucagon caused a rise of 13.7%, implying increased glucagon sensitivity at 5 degrees C. The glucagon-induced enhancement of VO2 was abolished by concurrent administration of noradrenaline.     

Lack of pressor effect of dopamine in the pentobarbital-anesthetized rat

The blood pressure and heart rate responses to intravenous dopamine infusion at 2.5, 5.0 and 10.0 micrograms.min-1 X 100 g-1 were studied in conscious and pentobarbital-anesthetized Sprague-Dawley rats. In the conscious rats, dopamine caused a significant dose-related increase in the mean arterial blood pressure which was abolished in the anesthetized rats. The heart rate increased significantly only at the highest dose infused. The responses to equipressor doses of noradrenaline (40 ng.min-1 X 100 g-1) and phenylephrine (1.0 micrograms.min-1 X 100 g-1) were also suppressed in the anesthetized rats. The results suggest that pentobarbital anesthesia depresses the blood pressure response to dopamine infusion in the rat through a depression of activation of alpha-adrenoceptors.     

Einfluss des Licht-Dunkel-Wechsels auf den O2-Umsatz der Rattenleber

Summary Similar diurnal periodicity in oxygen consumption of liver slices in Wistar rats was observed as that previously found in Sprague-Dawley rats. The rate of oxygen consumption was low in the morning and high in the evening. After inversion of lighting regimes, the phase shifted and reached the reversal curve in about 30 days. On the basis of these findings, it is estimated that diurnal periodicity in oxygen consumption of liver slices is influenced by alteration of the periods of light and darkness. Liver glycogen rhythm showed a reversed correlation to that of oxygen consumption in both lighting regimes.     

The influence of hypertension upon the normal cardiovascular responses to hemorrhagic hypotension and shock

The data suggest that rats genetically inbred to be hypertensive (SHR) are less able to compensate for hemorrhage and shock than their normotensive controls (WKY). Two reasons for this genetic dysfunction are: 1) SHRs seem to depend more on innervated alpha 1 than noninnervated alpha 2 adrenoreceptors for vasoconstriction; and 2) the vascular smooth muscle hypertrophy noted in SHRs may interfere with effective vasoconstriction.     

Diuretic and antifeedant actions byManduca sexta diuretic hormone in lepidopteran larvae

Neuroendocrine disruption of water balance in insect larvae was evaluated as the basis for a new approach to pest insect control. Effects on water balance and food consumption were measured for larvae ofHeliothis virescens (cotton budworm) treated with syntheticManduca sexta diuretic neurohormone (MasDH). Synthetic MasDH (50–250 nM) caused dose-dependent increases in fluid secretion by larval Malpighian tubules in vitro; higher concentrations resulted in lower fluid secretion. Last instar larvae injected with 20–100 pmol MasDH exhibited increasing weight loss. Larvae injected with 500 pmol MasDH dramatically reduced both water excretion and food consumption by 70%. These latter results indicate that high titers of diuretic hormone can suppress feeding damage by larval insects by depressing water excretion and food consumption.     

Responses to stimulation of the peripheral end of the right splanchnic nerve in the conscious calf

Summary The ratio at which adrenaline and noradrenaline are released from the adrenal medulla in response to stimulation of the splanchnic nerve has been established in the conscious calf. The proportion of adrenaline: noradrenaline was closely similar to that in which the 2 amines are stored in the gland and released in response to other stimuli in conscious, but not anaesthetized, calves.Acknowledgments. This work has been supported by a grant from the Agricultural Research Council, and we are also indebted to Dr D.M. Burley (Ciba) for his continued support. It is a pleasure to acknowledge the skilled technical assistance provided by Mr P.M.M. Bircham.