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K E Cooper

Publications and source records attributed to K E Cooper.

At least 19 recordsLinked to original sources

Vasopressin perfusion within the medial amygdaloid nucleus attenuates prostaglandin fever in the urethane-anaesthetized rat.

The antipyretic effect of arginine vasopressin (AVP) introduced into the ventral septal area (VSA) by push-pull perfusion was investigated in the urethane-anaesthetized rat. In addition, experiments were carried out to determine whether AVP could suppress fever when similarly perfused within the medial amygdaloid nucleus (meA). During push-pull perfusion of artificial cerebrospinal fluid within the VSA or meA, PGE1 injected intracerebroventricularly evoked fevers with respective magnitudes of 1.3 +/- 0.2 degrees C and 1.4 +/- 0.3 degrees C above baseline. Perfusion of AVP (6.5 micrograms/ml) within the VSA had significantly reduced the magnitude of PGE1 fever to 0.3 +/- 0.3 degrees C above baseline, while having no significant effect on afebrile colonic temperature. Perfusion of AVP (6.5 micrograms/ml) within the meA had significantly attenuated the magnitude of PGE1 fever to 0.7 +/- 0.2 degrees C above baseline, while having no significant effect on afebrile colonic temperature. These results support further the utility of the urethane-anaesthetized rat model for future investigations of the central control of fever and antipyresis. In addition, these data are consistent with the hypothesis that AVP may act within the meA as an endogenous antipyretic.

Alprostadil

Fever response of sheep in the peripartum period to gram-negative and gram-positive pyrogens.

We have measured body temperatures and serum iron concentrations of sheep in the peripartum period following administration of endotoxin and Staphylococcus aureus cell walls. Both the rise in rectal temperature and the fall in serum iron concentration following intravenous injection of S. aureus were the same immediately pre- and postpartum as they were 5 weeks after parturition. The rise in rectal temperature following intravenous endotoxin injection immediately pre- and postpartum was significantly less than that of the same ewes 5 weeks later. However, the fall in serum iron concentration following endotoxin injection was significantly suppressed only prepartum. We conclude that fever is not suppressed in sheep in the peripartum period, but the response to endotoxin is suppressed, through complex processes incidental to the mechanism responsible for the maintenance of gestation and induction of labour.

Animals

Modulation of brown adipose tissue-mediated thermogenesis by lesions to the nucleus tractus solitarius in the rat.

Given that relatively little is known regarding the central control of brown adipose tissue (BAT)-mediated thermogenesis the present study assessed whether the direct pharmacological stimulation of beta- or alpha-adrenergic receptors located on the brown adipocytes would result in a typical thermogenic response following electrolytic lesions to the nucleus tractus solitarius (NTS). Bilateral electrolytic lesions to the NTS in the rat effectively disrupted the baroreceptor reflex arc. It was observed that the metabolic and temperature responses to either norepinephrine (1, 5, or 25 micrograms/kg/min) or to the beta-agonist isoproterenol (0.5 micrograms/kg/min) were significantly attenuated in the NTS-lesioned rats relative to the control animals with an intact baroreflex. Conversely, the cardiovascular effects of norepinephrine or of the alpha-agonist phenylephrine (10 micrograms/kg/min) were enhanced in the NTS-lesioned animals. The results suggest that the functional capacity of the brown adipocytes was reduced following NTS lesions and points to an alteration in the ability of beta-receptors to respond to pharmacological stimulation with a typical thermogenic response.

Adipose Tissue, Brown

Cyclic GMP regulation of a voltage-activated K channel in dissociated enterocytes.

Enterocytes from the intestinal epithelium of the winter flounder were isolated by collagenase digestion and incubated in flounder Ringer solution. Conventional whole-cell and amphotericin-perforated whole-cell recording techniques were used to characterize the properties of a voltage-activated K current present in dissociated cells. Resting membrane potentials and series resistances were significantly lower (from -23 to -39 mV and 29 to 13 M omega, respectively) when amphotericin was used to achieve the whole-cell configuration. When cells were placed in flounder Ringer solution, held at -80 mV and subsequently stepped to a series of depolarizing voltages (from -70 to 0 mV), an outward current was observed that exhibited inactivation at voltages above -20 mV. This current was sensitive to holding potential and was not activated when the cells were held at -40 mV or above. When cells were bathed in symmetric K Ringer solution and the same voltage protocol was applied to the cell, inward currents were observed in response to the negative intracellular potentials. Reversal potentials at two different extracellular K concentrations were consistent with K as the current-carrying ion. BaCl2 (2 mM) and CsCl (0.5 mM) both produced voltage-dependent blockade of the current when added to the bathing solution. Charybdotoxin (300 nM extracellular concentration) completely blocked the current. The IC50 for charybdotoxin was 50 nM. Cyclic GMP inhibited the voltage-activated current in flounder Ringer and in symmetric K Ringer solution. The cyclic GMP analog, 8-Br cGMP, lowered the threshold for voltage activation and potentiated inactivation of the current at voltages above -40 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphotericin B

Nucleus tractus solitarii lesions alter the metabolic and hyperthermic response to central prostaglandin E1 in the rat.

1. Given that the nucleus tractus solitarii (NTS) may regulate the ability of brown adipose tissue to evoke non-shivering thermogenesis and that brown fat may mediate the rise in whole-body metabolism observed following central pyrogen administration, we assessed whether interruption of baroreceptor afferents coursing though the NTS would interfere with the ability of prostaglandin E1 to evoke a normal fever response profile. 2. Infusion of 150-600 ng of prostaglandin E1 (PGE1) into a lateral cerebral ventricle of the conscious rat resulted in a rise in core temperature, and also an increase in whole-body metabolic rate, brown adipose tissue temperature, arterial blood pressure and heart rate. 3. Following bilateral electrolytic lesions to the NTS, resting core and brown fat temperatures, metabolic rates, blood pressures and heart rates in the NTS-lesioned animals were comparable to control rats. However, the PGE1-evoked increase in metabolic rate, along with the rise in core and brown adipose tissue temperatures and heart rate were attenuated. The pressor response was, however, enhanced, possibly due to the demonstrated interference by the lesions with normal baroreflex control. 4. The findings suggest that the nucleus tractus solitarii region of the rats' brain may be important in mediating the thermogenesis evoked by central PGE1.

Adipose Tissue, Brown

Contribution of brown adipose tissue to central PGE1-evoked hyperthermia in rats.

The relative contribution of several effector systems to a prostaglandin E1-(PGE1) evoked hyperthermia was examined. Infusion of 150 ng of PGE1 into a lateral cerebral ventricle increased core temperature and whole body metabolic rate, brown adipose tissue temperature, systolic blood pressure, and heart rate. Pretreating the animals with a nonselective beta-antagonist propranolol (1 mg/kg iv in 0.3 ml followed by 3 mg.kg-1.h-1 in 0.3 ml/h) not only attenuated the rise in metabolism observed after the central administration of 150 ng PGE1 but also diminished the elevation in both core and brown fat tissue temperatures as well as the increase in heart rate. Pretreating the animals with the alpha-antagonist prazosin (2 mg/kg im followed by 50 micrograms.kg-1.h-1 iv in 0.3 ml/h) somewhat reduced the rise in whole body metabolism, suppressed the elevation in core temperature, but failed to alter the rise in brown adipose tissue temperature normally seen after the central administration of PGE1. Moreover, both the rise in systolic blood pressure and heart rate were attenuated when the PGE1 administration was preceded by prazosin. These results suggest that brown adipose tissue is an important effector organ responsible for mediating the hyperthermic response observed after the intracerebral injection of PGE1. In addition, the results indicate that alterations in vasomotor tone may also be important in producing or sustaining the elevated core temperature found after a pyrogen administration.

Adipose Tissue

The effectiveness of arginine vasopressin and sodium salicylate as antipyretics in the Brattleboro rat.

The infusion of either 30 micrograms/microliters (approx. 100 micrograms/kg/h) of sodium salicylate or 10 ng/microliters (10(-5) M) arginine vasopressin within the ventral septal area of the Brattleboro rat brain reduced a centrally induced prostaglandin E1 (PGE1) hyperthermia when compared with infusions of artificial cerebrospinal fluid. Conversely, the infusion of a related peptide, oxytocin (10 ng/microliters (10(-5) M), or 33 ng/kg/h) failed to alter the rise in core temperature following the PGE1 injection. These results suggest that the vasopressin receptors reported to be present in the Brattleboro rat may respond normally to exogenously administered vasopressin, thus allowing for the antipyretic action. Moreover, the antipyretic effects of sodium salicylate suggest that aspirin-like drugs may induce the release of alpha-melanocyte-stimulating hormone which, in turn, attenuates the PGE1-evoked fever. Given recent evidence, however, which suggests that the Brattleboro rat may contain vasopressin both peripherally and within the brain, the antipyretic action of sodium salicylate may be alternatively explained through the endogenous release of vasopressin.

Alprostadil

Cerebrospinal fluid pressure in conscious rats during prostaglandin E1 fever.

Intraperitoneal body temperature was monitored from groups of 10 conscious adult male Wistar rats. The daily body temperature rhythm was determined, and an intraperitoneal body temperature dose response relationship was established for prostaglandin E1 (PGE1) delivered into a lateral cerebral ventricle (LCV). Cerebrospinal fluid pressure was measured by direct cannulation of a LCV. Heart rate, arterial and central venous blood pressure, and blood gases were also measured in groups of 10 animals. It was found that there was a daily rhythm in intraperitoneal body temperature that was higher at night than during the day but stable between 0800 and 1600 h. A significant temperature dose (20-2,000 ng)-response relationship was established for administration of PGE1 into the LCV. Cerebrospinal fluid pressure when measured from the LCV increased significantly during the "chill" phase of the PGE1-induced fever. Carotid arterial blood pressure also significantly increased at this time as did central venous pressure, particularly so with vigorous shivering. There was a significant fall in arterial CO2 partial pressure, a slight rise in pH, and no change in arterial O2 partial pressure. These data support the hypothesis that a significant increase in cerebrospinal fluid pressure occurs during the chill phase of a PGE1-induced fever in the conscious rat.

Alprostadil

Indomethacin-induced antipyresis in the rat: role of vasopressin receptors.

Infusion of 15 micrograms/microliters (approximately 120 micrograms/kg/h) of indomethacin within the ventral septal area of the rat brain significantly reduced a centrally induced prostaglandin E1 (PGE1) hyperthermia when compared with infusions of artificial cerebrospinal fluid. A bolus injection of a V1 receptor antagonist, d(CH2)5Try(Me)AVP, (200, 2000, or 20,000 pmol) within the ventral septal area had no effect of body temperature alone but did suppress the PGE1-induced fever. Similar bolus injections of the V1 receptor antagonist within the ventral septal area failed to alter the antipyretic action of indomethacin on the hyperthermia resulting from centrally administered PGE1. Central injections of a V2 receptor antagonist failed to alter either the PGE1-induced fever or the indomethacin-evoked antipyresis. The results suggest that the V1 receptor antagonist may exert non-specific neurodepressant effects which may interfere with the expression or production of PGE1 hyperthermia and may further mask any contribution of arginine vasopressin to the antipyretic effects of indomethacin.

Angiotensin Receptor Antagonists

Sodium salicylate: alternate mechanism of central antipyretic action in the rat.

Infusion of sodium salicylate (50.0 or 100.0 micrograms/microliters) into the ventral septal area (VSA) of the rat brain suppressed Prostaglandin-E1-induced hyperthermia. Infusion of artificial cerebrospinal fluid (aCSF) or 10.0 micrograms doses of salicylate did not. The suppression of intracerebroventricularly-induced (icv) Prostaglandin E1 (PGE1) hyperthermia was not due to a hypothermic action of salicylate since salicylate infusions given during cold exposure (10.0 degrees C) did not lower core body temperatures. A possible interaction between salicylate and endogenous arginine vasopressin (AVP) was investigated. Infusion of both salicylate (50.0 micrograms/microliters) and either AVP antiserum or AVP antagonist into the VSA resulted in PGE hyperthermias occurring at levels which were not different from control levels as opposed to enhanced hyperthermia (antiserum or antagonist alone) or suppressed hyperthermia (salicylate alone). These results are consistent with the notion that sodium salicylate infusions within the VSA enhance AVP action and thus bring about the attenuation of PGE-induced hyperthermia.

Alprostadil

Potassium channels in chick lens epithelium change with maturation.

Before hatching, chick embryos show a high incidence of inwardly rectifying potassium channels and calcium-activated potassium channels in the apical membrane of their lens epithelium. Subsequent to hatching, these channel types disappear while, at about the same time, a new calcium insensitive maxi potassium channel appears. This new channel shows several properties in common with the calcium-activated maxi potassium channels but is different in its conductive and gating properties.

Analog-Digital Conversion

A cation channel in frog lens epithelia responsive to pressure and calcium.

Patch-clamp recording from the apical surface of the epithelium of frog lens reveals a cation-selective channel after pressure (about +/- 30 mm Hg) is applied to the pipette. The open state of this channel has a conductance of some 50 pS near the resting potential (-56.1 +/- 2.3 mV) when 107 mM NaCl and 10 HEPES (pH 7.3) is outside the channel. The probability of the channel being open depends strongly on pressure but the current-voltage relation of the open state does not. With minimal Ca2+ (55 +/- 2 microM) outside the channel, the current-voltage relation is nonlinear even in symmetrical salt solutions, allowing more current to flow into the cell than out. The channel, in minimal Ca2+ solution, is selective among the monovalent cations in the following sequence K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+. The conductance depends monotonically on the mole fraction of K+ when the other ion present is Li+ or Na+. The single-channel current is a saturating function of [K+] when K+ is the permeant ion, for [K+] less than or equal to 214 mM. When [Ca2+] = 2 mM, the current-voltage relation is linearized and the channel cannot distinguish Na+ and K+.

Animals

Neurotransmitter effects on body temperature are modified with increasing age.

This study reports effects on body temperature, in two different age groups of Sprague Dawley rats, of intracerebroventricular (ICV) administration of prostaglandin E2, noradrenaline, serotonin, dopamine, and carbachol. Young animals (3-5 months) developed fevers in response to administration of prostaglandin E2 (+ 1.02 +/- 0.26 degrees C), while no significant changes in colonic temperature were observed in the older (15-18 months) group of rats. Noradrenaline (10.0 micrograms), caused a decrease in colonic temperature in the younger group of animals (-2.02 +/- 0.70 degrees C), but had no significant effects on the body temperature of the older group. Similarly, differences between the temperature responses of the young as compared with the older group of animals were observed following ICV administration of carbachol, dopamine and serotonin. These data suggest that the roles of these substances in the hypothalamic control of body temperature may be modified with increasing age.

Aging

Evidence supporting a role for endogenous vasopressin in natural suppression of fever in the sheep.

1. The antipyretic effect of arginine vasopressin (AVP) introduced into the brain by push-pull perfusion was investigated in the sheep. 2. Control perfusions with sucrose solutions had no effect on fevers induced by a bacterial endotoxin. Sucrose solutions containing AVP (4.0 microgram/ml.) perfused at 40 microliter./min had significant antipyretic activity, reducing the two peaks of the fever but had no effect on resting body temperature. 3. Loci in which AVP induced antipyresis were limited to the septal region about 2-3 mm anterior to the anterior commissure. 4. The amounts of AVP in perfusates from the septal region correlated negatively with changes in body temperature. 5. AVP administered I.V. did not lower fever. 6. AVP plasma levels correlated negatively with fever magnitude following premature birth induced by dexamethasone.

Animals