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A chronic, indwelling, tail arterial cannula was implated in conscious undisturbed rats for measurement of blood pressure and heart rate and for obtaining blood samples. As an index of sympathetic activity, plasma levels of catecholamines in arterial blood of conscious animals were assayed by a radioenzymatic, paper-chromatographic procedure. Blood pressures of unrestrained spontaneously hypertensive (SHR) rats in their home cages (161 +/- 3/141 +/- 4 mmHg) were not different from those of pentobarbitol-anesthetized, hypertensive animals but were about 25 mmHg lower than awake animals during the restraint required for the tail-cuff procedure. Basal levels of plasma catecholamines in awake, undisturbed or in pentobarbital-anesthetized animals were similar in age-matched SHR and normotensive Wistar-Kyoto (WKY) rats. SHR rats were shown to have greater increase in plasma catecholamines than WKY rats during forced immobilization or restraint for indirect measurement of blood pressure.

MHPG is formed from norepinephrine metabolized throughout the body; its levels in plasma reflect total norepinephrine metabolism. Over half of the MHPG, is converted to VMA. Less than 20% of MHPG is derived from brain norepinephrine and urinary excretion of this metabolite cannot be used as a measure of brain norepinephrine metabolism. Because unconjugated MHPG is readily diffusable, there is a free exchange of this metabolite among plasma, cerebrospinal fluid, and nerve tissues (including brain and spinal cord). The CSF MHPG levels, after appropriately correction for the plasma contribution of the metabolite, reflect its rate of formation in the central nervous system.

Cancer patients, treated with hyperthermia (to 41.5 degrees C) under thiopental and fentanyl anesthesia, had smaller increases in heart rate and cardiac index and lesser decreases in mean arterial pressure than those reported in normal volunteers. At basal body temperature anesthesia did not alter catecholamine levels. Increasing body temperature to 39.5 degrees C and 41.5 degrees C resulted in parallel increases in heart rate and cardiac index that were directly related to the increases in plasma norepinephrine levels. At basal temperature cutaneous venous plasma norepinephrine levels exceeded those of arterial; mixed-venous plasma levels were intermediate. At 39.5 degrees C and 41.5 degrees C there were sequential increases in plasma norepinephrine. The increases in mixed-venous and arterial norepinephrine were significantly greater than in cutaneous venous blood. The differential increases in norepinephrine levels in cutaneous venous, mixed-venous, and arterial blood indicate that during hyperthermia sympathetic nerve activity in skin is decreased while that in other areas is increased, suggesting that alterations in sympathetic activity modulate the hemodynamic changes that attend hyperthermia in man.

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Results and discussion. Quantitation of proliferative cell activity (table) yielded 2.67 cpm per crypt (wet wt). This figure can be used for further quantitation since dry vs wet weights have no bearing on this number. The cpm per mg data was 1.01 • 104 dry wt and 1.60= 103 wet wt. Proliferative cellsper mg were calculated to be 1.71 = 105 dry wt and 2.71= 10~wet wt. The data between these groups are consistent since the number of proliferative cells per crypt is 4.5 = 101 for both dry and wet parameters. Our calculations on the quantitation of proliferative activity of the intestine give figures which are lower by at least a power of ten than those of Hagemann et al. m for the mouse. This difference was true for both dry and wet weights. There was a substantial difference in sampling since our samples consisted of mucosal scrapings only and did not include the muscle layer. Elimination of the weight of the muscle layers which take up little 3HTdr would result in a higher uptake per mg in animals with the same 987 proliferative rates. Our figures are nevertheless lower and thus indicate a substantial decrease in proliferative activity in the gerbil gut. Two factors which may affect the various parameters were analyzed: age and diurnal variation. Both variables were carefully monitored. Crypt size might also affect the cpm/ mg determination, since the gerbil's crypt size is 181 cells as compared to 450 in rats 13 and 500 in mice 14.The gerbil, Meriones unguiculatus, is an important addition to cell kinetic modeling. It has been useful in grafting experiments, and may provide a base for the establishment of a number of new transplantable tumor lines. The gerbil has been shown to have high radioresistance ll'n and an extremely slow intestinal transit time 7-9.The slower proliferative activity in the small intestine of the gerbil may prove useful in models for studies on the small intestine and on radioresistance. Summary.Our experiments have shown that using microwave irradiation to sacrifice the animals prevents further postmortem synthesis of prostaglandins in the rat brain.In this preliminary study the possible correlation between total prostaglandin E and E 2 contents have been evaluated in rat brain hypothalamus after decapitation in comparison to the basal values obtained by using the microwave technique for sacrificing animals. Male Sprague-Dawley rats (250-350 g) were anesthetized with sodium pentobarbital (50 mg/kg i.p.) to avoid possible effects on prostaglandin content caused by the brief immobilization stress that occurs in the microwave technique (Poddubiuk, unpublished results) and killed between 02.00 h and 14.00 h by decapitation with a guillotine at 24 ~ or by microwave radiation by focusing the microwave radiation on the head for 5 sec (5 kW; 2450 MHz, General Medical Engineering, Peabody, Mass.). Brains were removed and placed on an ice-cooled plate for dissection. Hypothalami were used for further procedures. Prostaglandins were extracted by homogenizing 200 mg of tissue in a mixture of 1 ml 0.9%...

1 Guinea-pig right atria were labelled with [3H]-noradrenaline or [3H1-dopamine before superfusion in a flow-cell. Choice of label did not significantly alter either the relationship between 3H-efflux and number of electrical field pulses or the inhomogeneity of labelling. 2 The relationship between 3H-efflux and frequency of 4 field pulses (0.125 -2 Hz) was hyperbolic and similar to the tachycardia-frequency relationship measured simultaneously. No evidence was found for a U shaped 3H-efflux-frequency relationship (Story, McCulloch, Rand & Standford-Starr, 1981). 3 Phentolamine (1 JiM) did not alter the 3H-efflux or atrial rate responses to 4 field pulses at stimulus levels that gave 50-60% of the maximum rate response. 4 In the presence of neuronal uptake inhibition (desipramine, DMI0.1 gsM), rate and 3H-efflux responses to 4 field pulses were enhanced at all frequencies and were further increased by phentolamine. 5 In the absence of DMI, prolonged trains of field pulses (8 and 12 pulses) at low frequency (0.25 Hz) were not sufficient to activate auto-inhibitory feed-back. At 2 Hz phentolamine enhanced both 3H-efflux and rate responses at 12 field pulses. 6 We conclude that in guinea-pig right atrium auto-inhibitory feed-back plays little role in the modulation of transmitter release at levels of stimulation that cause 50-60% of maximum tissue response. This is because neuronal uptake normally prevents synaptic concentrations of noradrenaline from activating prejunctional c2-adrenoceptors. Stimulation sufficient to induce a nearmaximal response or the presence of neuronal uptake inhibition are necessary to evoke autoinhibitory feed-back. IntroductionThe prejunctional Mc2-adrenoceptor has been considered to be part of an inhibitory feed-back loop whereby transmitter released from sympathetic nerve endings diminishes subsequent transmitter release (Starke, 1977;Rand, McCulloch & Story, 1980;Langer, 1981). Auto-inhibitory feed-back has been thought to modulate transmitter release from pulse to pulse (Rand, Story, Allen, Glover & McCulloch, 1973 Angus & Korner (1980) recently challenged the importance of auto-inhibitory feed-back under moderate conditions of sympathetic stimulation. They found in the guinea-pig isolated right atrium that the tachycardia response was not influenced by pretreatment with phentolamine and yohimbine at sympathetic stimulus strengths that raised the rate up to 50% of the maximum response. This was investigated further by Story et al. (1981) absence of auto-inhibitory feed-back under stimulus conditions similar to those employed by Angus & Korner (1980). But they defined two specific conditions under which sympathetic transmission was altered by auto-inhibitory feed-back: (1) a maximum interval between successive stimuli (4 -8 s) and (2) an adequate length of stimulus train of at least 1.5 s at higher frequencies (2 Hz).Surprisingly with stimulation by 4 pulses Story et al. (1981) observed a U-shaped relationship between the frequency of stimulation and 3H-efflux, which contrasted ...

A recent study demonstrated that dextroamphetamine has an effect in normal prepubertal boys similar to that seen in hyperactive children. The purpose of the present study was to see whether the effects of caffeine are similar to those of amphetamine in normal children. The authors observed 19 prepubertal boys following administration of a single dose of placebo, 3 mg/kg of caffeine, and 10 mg/kg of caffeine in a double-blind, crossover design. Caffeine produced increased vigilance and decreased reaction time, as does amphetamine. Unlike amphetamine, however, the higher dose of caffeine did not have a motor calming effect but increased motor activity. Separate biological systems, therefore, may be differentially affected by the two substances.