The participation of nitric oxide in the facilitator effect of arginine vasopressin on memory.

In this study we tested the hypothesis that nitric oxide (NO), which function as a novel type of inter-cellular messenger in the central nervous system (CNS) participated in the facilitator effect of arginine vasopressin (AVP) on learning and memory. Recent investigations have provided evidences that inhibition of NO synthesis attenuated the vasodilatation caused by AVP, and inhibited the improvement of learning and memory evoked by angiotensin II. AVP as well as pharmacologically produced increase in endogenous NO facilitates the consolidation of shock avoidance learning. We evaluated the behavioural effects of AVP at dose 1 microgram after the inhibition of NOS by NG-nitro-L-arginine methyl ester (L-NAME) at dose 10 micrograms, and after the injection of endogenous donor of NO -L-arginine- 10 micrograms in the retrieval of passive avoidance situation, and in consolidation of active avoidance responses. The locomotor activity of all investigated drugs was tested in the open field test. AVP facilitated the recall of passive avoidance responses and consolidation of active avoidance responses. Neither the increase of NO concentration after the injection of L-arginine nor the decrease of NO after the inhibition of NOS by L-NAME changed the behavioural effects of AVP. L-arginine increased the psychomotor behaviour and L-NAME decreased the activity of animals in the "open field" test. L-arginine itself improved the consolidation of active avoidance responses. Our results indicate that central action of AVP is probably independent of NO concentration in the brain.

Nitric oxide in learning and memory.

The role of nitric oxide in the central nervous system is described. The main part of this article concerns the problem of learning and memory.

Behavioural activity of angiotensin II (3-7)4Phe--analogue of natural fragment 3-7 of angiotensin II.

A study was made of the influence of pentapeptide 3-7 angiotensin II [AII(3-7)], its analogue 3-7(4)Phe [AII(3-7)4Phe] and angiotensin II (AII) on the behaviour of adult male rats. The motility, stereotypy, spatial performance, learning of conditioned and passive avoidance responses allowing to avoid aversive stimulation were estimated. Examined peptides at the dose 1 nmol injected intracerebroventricularly 15 min before the experiment did not produce specific changes in psychomotor activity in the "open field" test and in retention of the spatial task in the Morris water maze. The rate of acquisition of conditioned avoidance responses was stimulated by AII(3-7)4Phe, AII(3-7) and AII administration. In the passive avoidance situation AII improved retention of the responses whereas analogue AII(3-7)4Phe and fragment 3-7 caused similar though less pronounced effect. All the peptides applied immediately before the experiment intensified stereotypy, a behaviour evoked by of apomorphine-1 mg/kg and amphetamine-7.5 mg/kg intraperitonealy injection. These results show similar psychotropic activity of analogue AII(3-7)4Phe, comparable with the activity of natural fragment 3-7 of angiotensin II.

High resolution multi-temperature sensors for biomedical application.

A temperature sensor array was designed in order to study local temperature variations and temperature gradients in biological samples. The sensor probe was inserted in the optical cortex of rabbits in order to study temperature changes during normal brain activity as well as under artificial ventilation conditions. Temperature sensitive areas of 0.14 mm x 0.1 mm are arranged in a row with interdistances of 0.4 mm yielding high spatial resolution. A temperature resolution of 0.1 mK and a 90% response time of maximum 3 milliseconds was obtained utilizing the high temperature dependence of 2%/K of the conductivity of vacuum evaporated germanium films. The sensor is passivated by a 1 micron thick PECVD-silicon nitride layer and can be placed on glass-, alumina- and polymer substrates. For brain tissue studies, in order to minimize tissue damage the temperature sensors were placed on a 0.1 mm thick needle-shaped glass substrate. A sensor element mounted on a glass substrate and immersed in water showed a self heating of less than 5 mK due to the applied measurement current of 2.1 microA.

Circannual variations in blood pressure, urinary catecholamine excretion, plasma aldosterone, and serum sodium, potassium, calcium, and magnesium in children 11 +/- 1.5 years of age.

A total of 194 clinically healthy children 11 +/- 1.5 years of age were studied during different seasons. Systolic and diastolic blood pressure were determined by auscultatory endpoints, and blood and urine were collected at 4-hr intervals over a 24-hr span. Urinary norepinephrine, epinephrine, and dopamine were determined by HPLC, plasma aldosterone by RIA, serum sodium and potassium by ion-specific electrode, and calcium and magnesium by colorimetry. The circadian means showed statistically significant circannual variations in all variables except epinephrine. The highest circadian means of systolic and diastolic blood pressure and of urinary norepinephrine occurred during winter; the highest values of plasma aldosterone, serum potassium, and urinary dopamine were found in fall, those of serum calcium and magnesium during the summer, and that of serum sodium in spring. Circannual rhythms characterize functions related to blood pressure regulation in children. The circannual elevation of blood pressure (within the usual range) and of norepinephrine were both found to occur in winter. This time relation may have a functional significance, although a causal relationship is not proven by the temporal coincidence of two rhythms.

Chronobiology of catecholamine excretion in different age groups.

Urine was collected at 4-hr intervals over a 24-hr span in 87 boys and 106 girls 11 +/- 1.5 years of age and over one or several 24-hr spans in 62 elderly men and in 85 elderly women 77 +/- 8 years of age. Epinephrine, norepinephrine, and dopamine were determined by HPLC. The data were analyzed by cosinor and by one-, two-, and three-way ANOVA. Children and elderly subjects showed circadian rhythms of urine volume and of the excretion of norepinephrine, epinephrine, and dopamine. While the urine volume was higher in the elderly subjects than in the children, norepinephrine, epinephrine, and dopamine excretion in the girls and epinephrine in the boys showed a statistically significantly higher mesor than in the elderly subjects of the same sex. There was a sex difference, with lower values in all variables in the girls and women compared to their male counterparts; the circadian amplitudes of norepinephrine, epinephrine, and dopamine in the girls and of epinephrine in the boys were higher than the circadian amplitudes in the elderly subjects. The circadian timing in urinary excretion between the elderly subjects and the children was different, with a consistent phase delay; the acrophase of the circadian rhythm in the elderly subjects moved in the night hours. In contrast, there was no age difference in the acrophase of norepinephrine and epinephrine excretion or in dopamine in the females. In the males, the circadian rhythm in dopamine excretion in the elderly subjects did not quite reach statistical significance at the P less than 0.05 level. Circannual variations with high values in winter and low values in spring and summer were found in norepinephrine excretion in boys, girls, and elderly women, but not in elderly men. In neither age group was there a statistically significant seasonal variation in epinephrine. Only in girls was a statistically significant circannual rhythm in dopamine excretion found, with highest dopamine values in the fall and lowest values in winter and spring.

Peculiarities of the endocrine time structure in noninsulin-dependent adult-onset (type II) diabetes mellitus.

Twenty noninsulin-dependent elderly diabetic patients, ten of whom were treated by oral hypoglycemic agents and ten of whom were regulated by diet alone, and 20 clinically healthy subjects matched for age, sex, height, and weight were examined with six blood and six urine samples at 4-hr intervals over a 24-hr span. Plasma ACTH, cortisol, aldosterone, and dehydroepiandrosterone-sulfate (DHEA-S) were determined by radioimmunoassay (RIA); epinephrine, norepinephrine, and dopamine in urine were determined by high-pressure liquid chromatography (HPLC); and magnesium in urine was determined colorimetrically on a DuPont ACA. There were a number of changes in some of these functions in type II diabetic patients with and without oral hypoglycemic agents that appear to be of interest. The circadian mean in plasma ACTH concentration in diabetic patients with and without oral hypoglycemic agents is significantly higher than in matched nondiabetic controls. The plasma aldosterone concentration is similar in type II diabetics treated by diet only and in matched controls but is statistically significantly elevated in patients on oral hypoglycemic agents. Correspondingly, the urinary excretion of sodium in type II diabetic patients on oral hypoglycemic agents is lower than in matched controls. The plasma cortisol concentration is unchanged in type II diabetic patients treated by diet alone but shows a slight increase in patients on oral hypoglycemic agents. The circadian means of plasma DHEA-S concentration is slightly higher in diabetic patients with and without oral hypoglycemic agents than in matched controls. This elevation, however, does not quite reach the 95% level of statistical significance. Urinary norepinephrine excretion in type II diabetic patients is similar to that in matched controls. The urinary epinephrine excretion in diabetics with and without oral hypoglycemic agents, however, was lower than in controls, and the urinary excretion of dopamine was higher in the diabetics. The urinary magnesium excretion in type II diabetic patients was lower than in matched controls.

An improved method for the extraction of endogenous platelet serotonin.

Investigations of blood platelet serotonin content, turnover, metabolism, and secretion require sensitive methods for accurate measurement of the amine. The present study has sought a simple, efficient procedure for extracting total platelet serotonin which could also be used for analysis of other platelet chemical constituents. ZnSO4 precipitation, the standard technique for extracting 5-HT, failed to recover total platelet serotonin despite physical and chemical manipulations to improve its availability. Perchloric acid extraction was found to be more efficient, resulting in significantly increased values for endogenous platelet serotonin and recovery of 97 per cent of standard amounts of 5-HT added to platelet pellets. In addition, the perchloric acid extracts could be used for analysis of other platelet constituents such as adenine nucleotides. The improved procedure eliminates the need for large numbers of replicate samples for several assays and, at the same time, provides a more sensitive method for recovery of total platelet serotonin. It may also prove valuable for prolonged in vitro experiments in which extraction must be followed by additional isolation procedures in order to separate indole metabolites of serotonin from the amine for specific quantitation.