Sex- and age-related changes in catecholamine metabolism and release of rat adrenal gland.

To examine the possible existence of changes in the adrenal catecholaminergic activity during aging, we analyzed the adrenal content of catecholamines (CA) and the activities of selected enzymes involved in their metabolism as well as the basal and the K+-stimulated release of these CA in incubated adrenal tissue of aged (greater than 22 months) and young (2 months) rats of both sexes. Adrenal contents of norepinephrine (NE) and epinephrine (E) of male rats were unaltered in aging, although aged males showed an increased activity of tyrosine hydroxylase (TH) and a decrease in phenylethanolamine-N-methyl transferase (PNMT) activity. In addition, the in vitro release of both CA as well as their content in the incubated adrenal tissue were higher in aged males than in young animals. However, the response of the adrenal of aged males to incubation with stimulatory concentrations of K+ was significantly lower than that observed in young males. Aged females showed increases in the adrenal content of E, although the activities of TH and PNMT were unaltered. As in aged males, the in vitro release of CA from incubated adrenal tissue was higher in aged females than in young rats, but the CA amounts measured in the incubated tissues were similar. Moreover, the response to stimulatory concentrations of K+ was lower in aged females than in young animals. In summary, these results clearly indicate that adrenal catecholaminergic activity is enhanced during aging, which could have important consequences for physiological functions regulated by the adrenal secretion. Also, some differences in the effects of aging could be observed between males and females.

Changes in the catecholamine metabolism in the adrenal medulla of male hamsters with experimental hyperprolactinemia.

1. Prolactin (PRL) can play a role as a physiological modulator of adrenal medulla function in several rodents. 2. We have examined the effects of hyperprolactinemia induced by ectopic pituitary grafts in Syrian hamsters on the adrenal medulla contents of catecholamines (CA) and their metabolites, as well as on the activities of several enzymes involved in the metabolism of these amines. 3. Increases in the peripheral levels of PRL in these animals were associated with decreases in adrenal medulla weight and increases in adrenal medulla contents of norepinephrine, epinephrine and vanilmandelic acid, the main degradative metabolite of CA, while adrenal medulla contents of the O-methylated derivatives of CA, normetanephrine and metanephrine, were unaltered. 4. These changes were correlated with increases in the adrenal medulla activity of monoamine oxidase, while the activities of tyrosine hydroxylase, phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase were unaltered. 5. These results indicate that PRL is able to act on the adrenal medulla of hamsters by increasing the ability of these cells to metabolize CA via oxidative deamination.

Effects of estrogens and progesterone on the catecholaminergic activity of the adrenal medulla in female rats.

Some reports in the literature allow to suspect the existence of an effect of sexual steroids on the adrenal catecholamines. To test this possibility, we have examined the catecholaminergic activity in the adrenal medulla of normal cycling rats in three phases of estrous cycle and of ovariectomized (OVX) rats injected with pharmacological doses of estradiol (ES), 2-hydroxyestradiol (HE) and/or progesterone (P). Adrenomedullary content of norepinephrine (NE) was similar during the estrous cycle, while epinephrine (E) content was increased during diestrous. This increase was concomitant with an increased phenylethanolamine-N-methyltransferase (PNMT) activity. Moreover, the monoamine oxidase (MAO) activity was significantly increased during proestrous, while the catechol-O-methyltransferase (COMT) activity was significantly decreased during estrous. In addition to these observations, ovariectomy caused a significant reduction of the E/NE ratio and of COMT and MAO activities. Administration of ES to OVX rats increased the E content, the E/NE ratio and the COMT activity as compared to vehicle-treated OVX rats. Administration of P to OVX animals led also to a significant increase of the E/NE ratio and of the COMT activity but not of the E content, while the administration of this steroid to OVX rats previously treated with ES only increased the COMT activity. Finally, administration of HE caused non-significant changes in NE and E contents and in MAO, COMT and PNMT activities. We can conclude that sexual steroids seem to be able to modify the catecholamine metabolism in the adrenal medulla and, hence, they could alter the ability of this gland to store and release these amines.

Induction of the synthesis of thymidine kinase by aldosterone in the kidney of the immature male rat.

Thymidine kinase activity was studied in kidneys from immature male rats after administration of aldosterone. Kinetic studies showed that the enzyme activity reached its maximum level 24 h after aldosterone injection. That increase was specific for aldosterone and could be related to the synthesis of new molecules of enzyme.

Modulation of myosin isoenzyme populations and activities of monoamine oxidase and phenylethanolamine-N-methyltransferase in pressure loaded and normal rat heart by swimming exercise and stress arising from electrostimulation in pairs.

The question of whether the effects of physical exercise on the heart of 15-weeks normotensive and hypertensive rats can be modulated by additional stressors was studied. Intermittent swimming (33-35 degrees C water, maximum 2 X 1.5 h/day, 2-6 weeks) was employed as a model of exercise. Electrostimulation of rats in pairs (maximum 2 X 1.5 h/day, 6 weeks) served as a model leading predominantly to stress. When the above procedures were combined, electrostimulation in pairs was performed in one session and was followed up by swimming. The myosin isoenzyme population was used as a marker of changes in contractile performance of myofibrils. Activities of the catecholamine-degrading enzyme monoamine oxidase (MAO) and the adrenaline-synthesizing enzyme phenylethanolamine-N-methyltransferase (PNMT) served to monitor chronic alterations of catecholamine turnover in myocardium. Redistribution in favour of VM-1 (ventricular myosin isoenzyme 1) occurred as early as 2 weeks after the onset of intermittent swimming and was observed under several experimental conditions. The redirection of genetic expression of the isoenzymes was not linked to the presence of an increased ratio of right to left ventricular weight, most probably arising from intermittent hypoxia during drownproofing. The myosin isoenzyme population of swimming spontaneously hypertensive rats (SHR) resembled that of sedentary Wistar rats. The enzyme activities of MAO and PNMT were both significantly reduced following 6 weeks intermittent swimming in Wistar rats and SHR. This can most probably be attributed to the exercise component of swimming which, on average, led to reduced catecholamine turnover in heart. Electrostimulation of rats in pairs for 6 weeks, which resulted in aggressivity and aggressions, did not alter the myosin isoenzyme population in Wistar rats; in SHR, it further augmented the proportion of VM-3 (ventricular myosin isoenzyme 3), which had already increased in the sedentary state. Furthermore, electrostimulation increased PNMT activity, but did not affect MAO activity. Electrostimulation in pairs, followed by swimming, altered the myosin isoenzyme population in the same way as did swimming alone. However, the activities of PNMT and MAO seemed to be governed by the routine involving stress and not by the exercise routine. This demonstrates that stressors supplementing exercise can decisively modify or even prevent reactions of the organism in response to exercise.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer simulation and experimental analysis of unipolar epicardial potentials in relation to the direction of propagation of the excitation.

A theoretical model for computer simulation has been introduced to predict the unipolar epicardial potentials corresponding to the different angles of propagation of the excitation wavefront. The simulated waveforms were compared with those observed in the animal experiments. In these experiments three unipolar epicardial potentials and one intramural potential were recorded using a thumbtack electrode with and without bipolar epicardial pacing. The direction of the propagation of the excitation was determined from the arrival time of the recorded waveforms. There was a close correspondence between the observed and the simulated waveforms. Furthermore, it was attempted to establish a quantitative relationship between the unipolar potential waveshape and the angle of propagation theta of the excitation. The difference between the positive and the negative peak normalized by the peak-to-peak height was used to define the change in the waveshape. A distinct relation was found to exist between the normalized difference R and the angle theta for the simulated potentials. There was a good correlation (r = 0.96 for n = 85) between angle theta 1 calculated from the arrival times and theta 2 determined from R, which suggest that the angle theta can be estimated from the unipolar epicardial potentials alone, without using any intramural electrode.

Hormone mediated changes in monoamine stores and regulation of enzymes of biosynthesis and metabolism in the rat adrenal gland. Influence of progesterone, estradiol, ACTH and testosterone administration.

The influence of daily injections, for 7 days, of 17-hydroxyprogesterone caproate (8 mg/100 g body weight pro die), of estradiol-17 beta 17-undecylate (1.2 mg/100 g body weight pro die) of testosterone enanthate (2 mg/100 g body weight pro die) and of ACTH (4 IU/100 g body weight pro die) to male Wistar rats, weighing 200 g, were investigated. Monamine storage and regulation of enzymes phenylethanolamine N-methyl transferase (PNMT), monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) were studied in the adrenal glands. Results from testosterone treated rats were especially significant : the hormone administration decreased the stores of dopamine and norepinephrine (epinephrine precursors), stimulated PNMT and decreased metabolism of epinephrine by MAO and COMT. However, the adrenal content of epinephrine remained in the normal range. These findings suggest that uptake of epinephrine is accelerated in peripheral tissues by testosterone.