Stereological Changes in Rat Ventral Prostate Induced by Melatonin

Effects of melatonin on the ventral prostate of castrated rats supplemented with testosterone were studied using light microscopy. Stereological measurements were made of volume fractions of acini and stroma and surface fractions of glandular epithelium. From these figures and the weights of the glands, the volumes and surface areas were calculated, as well as the mean epithelial heights, mean acinar diameters, and mean distances between glandular acini. Doses of melatonin were varied, to verify its physiological and pharmacological effects. Castration without hormonal treatments produced atrophic changes, with decreases in acinar and stromal volume and widenings in the mean distances between the acini. None of these measurements differed among intact controls, sham-operated controls, and testosterone-supplemented castrated rats. In the castrated rats receiving both testosterone and melatonin, however, there were changes according to the doses of melatonin given. The animals receiving low doses of melatonin (50 and 400 micrograms daily) showed significant decreases in the volumes of the stroma and epithelium and the height of the epithelium. These stereological changes occurred without a significant reduction in the prostatic weights. The animals receiving the higher dose (800 micrograms daily) of melatonin showed no difference in any measurement compared with those of the testosterone-supplemented castrated rats. In rats receiving 2,000 micrograms of melatonin daily, there were significant reductions in the weights of the prostates and the volumes of the acini. These results suggest a direct action of melatonin on the ventral prostate, and the effects depend on the dose given.     

Effect of androgens on hypothalamic pro-opiomelanocortin

Testosterone and estradiol have been shown to affect the hypothalamic content of several pro-opiomelanocortin (POMC)-derived peptides in castrated male and female rats, respectively. It was unclear, however, whether the effects of testosterone on hypothalamic POMC were due to conversion by aromatization to estradiol or whether there were independent androgen actions on hypothalamic POMC. In order to answer this question, the effect of treatment with the nonaromitizable androgen 5-alpha-dihydrotestosterone (DHT) on the concentration of beta-endorphin (beta-EP) in the medial basal hypothalamus (MBH) was studied in castrated male rats and compared to the effect of treatment with testosterone or estradiol. The concentrations of two other POMC-derived peptides, corticotropin-like intermediate lobe peptide (CLIP) and alpha-MSH were measured as well. Adult male rats were castrated and received either no treatment or treatment with subcutaneously implanted silastic capsules, containing either DHT, testosterone or estradiol, designed to produce steroid levels in a physiological range. After 4 weeks the mean concentration of beta-EP in the MBH of the untreated castrated rats was 1,640 +/- 56 fmol/mg protein. This was reduced significantly to 1,184 +/- 74 fmol/mg protein after DHT treatment (p less than 0.001). Similar reductions to 1,340 +/- 95 and 1,130 +/- 85 fmol/mg protein were noted after testosterone and estradiol treatment, respectively. The mean CLIP concentration of 1,870 +/- 73 fmol/mg protein in the untreated animals fell to 1,390 +/- 95 after DHT (p less than 0.001) compared to 1,520 +/- 105 and 1,260 +/- 101 after testosterone and estradiol treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The in-vitro transformation of [3H]dehydroepiandrosterone into its principal metabolites in the adrenal cortex of adult castrated male rats and following steroid treatment

The adrenal gland of castrated adult male rats metabolized [3H]dehydroepiandrosterone in vitro to delta 4-androsten-3,17-dione (4AD), testosterone, dihydrotestosterone (DHT) and 5 alpha-androstane-3,17-dione (5 alpha AD). Despite the low testosterone values, DHT and 5 alpha AD were higher 30 and especially 60 days after castration, with raised 4AD:testosterone and decreased testosterone:DHT ratios. The 5 alpha-reductase activity thus appears to increase with time after castration. Fourteen days after castration, 4AD was the only metabolite that was raised compared with intact animals, and testosterone was comparable in sham-operated and castrated rats. The administration of testosterone propionate to castrated rats restored testosterone values to those of intact rat adrenals, whereas 4AD values were greater. The administration of dihydrotestosterone propionate also yielded higher levels of 4AD, in the presence of a lower testosterone value. After administration of oestradiol benzoate, 4AD values were lower especially compared with the other hormone-treated groups, and there was an unexpectedly high testosterone value. These data indicate that the adrenal gland contributes to the production of androgens, as previously noted by Andò, Canonaco, Beraldi et al. (1988) who showed increased plasma 4AD and testosterone levels in adult male rats 30 days after castration. Furthermore, adrenal androgen production in castrated animals is differentially regulated by sex steroids.     

Hypothalamic-pituitary-testicular system and adrenocortical function.

Effect of intramuscular administration of ACTH or dexamethasone on blood serum levels of testosterone, LH and FSH was examined in intact and castrated, adult, male rats. Six IU ACTH or 1 mg dexamethasone were given daily for 7 days. Corticotrophin treatment had no influence on circulating testosterone, LH and FSH in intact or castrated male rats. Dexamethasone administration resulted in a slight elevation of serum FSH in intact animals but not in castrates. LH and testosterone remained normal in both intact and castrated animals injected with dexamethasone. Under our conditions of study the secretions from the adrenal gland appear to be insignificant for the regulation of pituitary secretion of gonadotrophins in the male rat.     

Pro-opiomelanocortin messenger RNA in hypothalamic neurons is increased by testosterone through aromatization to estradiol

We have previously demonstrated that neurons in the rostral arcuate nucleus expressing the messenger RNA (mRNA) for pro-opiomelanocortin (POMC) are responsive to modulation by physiological levels of testosterone. It is uncertain, however, whether testosterone's action is mediated through direct activation of androgen receptors or through aromatization to estradiol and subsequent binding to estrogen receptors. We examined this question by evaluating the effectiveness of estradiol and dihydrotestosterone (DHT), a nonaromatizable androgen, in reversing the castration-induced diminution of POMC mRNA in the arcuate nucleus. Using in situ hybridization, we measured POMC mRNA content within arcuate neurons of intact, castrated, castrated testosterone-replaced, castrated estradiol-replaced, and castrated DHT-replaced male rats. Adult male rats were castrated and implanted (s.c.) with a Silastic capsule filled to one of the following specifications: crystalline testosterone (30 mm; n = 4); 17 beta-estradiol (E2) diluted 1:1 with cholesterol (5 mm; n = 4); DHT (40 mm; n = 4); or empty (30 mm; n = 4). Control, sham-operated animals (n = 4) were left intact. Analysis of the results showed that following castration, POMC mRNA content was significantly reduced in cells of the arcuate nucleus (intact: 152 +/- 3 grains/cell vs. castrate: 110 +/- 3 grains/cell). Replacement with physiological levels of testosterone prevented the decline of POMC mRNA levels (castrated testosterone-replaced: 143 +/- 6 grains/cell), as did replacement with physiological levels of estrogen (castrated estrogen-replaced: 149 +/- 8 grains/cell). Treatment with DHT failed to prevent the postcastration decline in POMC mRNA content (castrated DHT-treated: 118 +/- 4 grains/cell).(ABSTRACT TRUNCATED AT 250 WORDS)     

Androgen-estrogen synergy in rat levator ani muscle: glucose-6-phosphate dehydrogenase

The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17 beta alone was ineffective. Combined treatment with estradiol-17 beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.     

Thyroid and gonadal regulation of hair growth during the seasonal molt in the male European badger, Meles meles L

In the male badger we showed that hair growth and molt are related to plasma testosterone and thyroxine cycles. We established the action of testosterone by castration and subcutaneous testosterone implants, and the action of thyroxine by thyroidectomy and dietary supplementation with thyroxine. The following groups of animals were studied: controls, thyroidectomized, thyroidectomized and thyroxine-treated, castrated, castrated and thyroxine-treated, thyroidectomized and castrated and thyroxine-treated, castrated and testosterone-implanted, and intact testosterone-implanted. In control animals, molt and hair growth occurred during the summer, with a maximum growth in autumn. Molt ended at the beginning of winter when the plasma testosterone level had started to rise, and began again after this level had started to decline. Both the start of molt and the period of maximum hair growth coincided with high thyroxine levels of about 20 ng/ml. Castration advanced molt and hair follicle activity, whereas testosterone implants delayed both molt and hair growth. In thyroidectomized badgers, neither hair growth nor seasonal molt was observed. However, when thyroxine levels were restored to 20 ng/ml or more by dietary T4 supplementation, molting was resumed in animals that had undergone either thyroidectomy or thyroidectomy plus castration. In those that underwent castration only, the molt was advanced leading to early hair growth further stimulated by the suppression of testosterone. Testosterone had an inhibitory effect on the molt--since testosterone implants in intact control animals delayed it by 4 weeks--but did not inhibit it completely. On the other hand, a T4-enriched diet advanced the date of the molt. However, the molt could not be induced, nor could hair follicle growth be reactivated, at all times during the annual cycle. Thus, in castrated animals. T4 enrichment of the diet in early January, at the end of the molt, caused follicle reactivation only toward the end of May, despite the lack of testosterone. This 18-week latency period from January to May might therefore constitute a "refractory period" in this species. The above findings show that the regulation of the seasonal molt and hair growth in the European badger involves both the thyroid and genital axes. This regulation is discussed in terms of joint control by the hypothalamus and pituitary governed, in turn, by an external factor--the photoperiod--considered to be the main synchronizer.     

Growth hormone-releasing hormone messenger ribonucleic acid in the hypothalamus of the adult male rat is increased by testosterone

Since intact adult male rats have higher GH pulse amplitude than do castrated animals and since GH-releasing hormone (GHRH) secretion is predominantly responsible for the production of these GH pulses, we hypothesized that testosterone stimulates GHRH synthesis in neurons of the hypothalamus. To test this hypothesis, we compared GHRH mRNA content in individual neurons of the arcuate (ARC) and ventromedial (VMH) nuclei among groups of intact (n = 3), castrated (n = 5), and castrated testosterone-replaced (n = 5) adult male rats. Cellular GHRH mRNA content was measured by using semiquantitative in situ hybridization with an 35S-labeled cRNA probe complementary to the coding sequence of rat GHRH mRNA. Castration resulted in an approximately 35% decline in GHRH mRNA signal relative to that in intact animals in both the ARC (P less than 0.005) and VMH (P less than 0.005). Replacement with testosterone at the time of castration completely prevented the decline in both areas. Testosterone can exert effects either through activation of the androgen receptor directly or through aromatization to estradiol; therefore, we also examined the effects on GHRH mRNA of replacement with 17 beta-estradiol (n = 5) or dihydrotestosterone (DHT), a nonaromatizable androgen (n = 4). Estradiol had no effect on the castration-induced decline in GHRH mRNA in either the ARC or VMH. In contrast, DHT partially prevented the postcastration decline in GHRH in the ARC (P less than 0.005), while having no statistically significant effect on GHRH mRNA in the VMH. These results clearly indicate that testosterone stimulates expression of GHRH mRNA in neurons of the hypothalamus. Furthermore, the failure of estradiol to substitute for testosterone and the ability of DHT to substantially support GHRH mRNA suggest that testosterone exerts its effects on GHRH gene expression predominantly through direct activation of the androgen receptor.     

Relation between circulating levels of testosterone lh and fsh in intact and castrated, adult, male rats after testosterone administration.

Serum levels of LH, FSH and testosterone were measured by radioimmunoassay in intact and castrated, adult, male rats after testosterone was administered subcutaneously for seven days in doses ranging from 25 to 200 mug per 100 g body weight per day. Such treatment increased circulating testosterone both in intact and castrated rats, but its effects on serum gonadotrophins were different in these animal groups. All doses of testosterone suppressed serum LH and FSH in the normal rat. In the castrates, treatment with the lowest dose of testosterone resulted in serum LH levels significantly above the high castrate levels, while serum FSH tended to drop. Administration of the highest doses of testosterone did not depress serum LH and FSH in the castrates to those of intact, normal animals, though serum testosterone in these castrates was much higher than in normal, male rats. It is concluded, that the sensitivity of the hypothalamic-pituitary system for daily, subcutaneous testosterone administration during seven days is not the same in the intact and castrated, adult, male rat and that testicular factors different from testosterone may play a role in regulating production and/or secretion of gonadotrophins by the hypophysis in male animals.     

Peripheral and central androgenic stimulation of sexual behaviour of castrated male rats

The effects of androgens on the maintenance and restoration of sexual behaviour (mounts, intromissions and ejaculations) of castrated male rats were studied. In the maintenance study the rats were treated during 5 weeks, starting one day following castration. Testosterone propionate maintained sexual behaviour at an almost normal level. The androgenoestrogen intermediate 19-hydroxytestosterone propionate was unable to prevent the decline in the number of ejaculations over the weeks although this hormone maintained the post-ejaculatory refractory period in those rats that ejaculated and also maintained normal sexual latencies. In the restoration study administration of testosterone propionate during 7 weeks to long-term castrated rats restored sexual behaviour to normal. 19-Hydroxytestosterone propionate treated rats displayed mounts but no other signs of sexual behaviour. The 5alpha-reduced androgen dihydrotestosterone propionate did not restore sexual behaviour. Testosterone propionate and dihydrotestosterone propionate stimulated peripheral target organs; 19-hydroxytestosterone propionate was ineffective in this respect. It has been suggested that testosterone might stimulate sexual behaviour in rats in two ways, i.e., via its aromatization to oestradiol in the brain, andy by stimulating growth of peripheral tissues via its 5alpha-reduction to dihydrotestosterone. In support for this view we have found that the combination of 19-hydroxytestosterone propionate and dihydrotestosterone propionate was effective in restoring the full pattern of sexual behaviour in castrated male rats.     

Effect of sex hormones on non-esterified fatty acids, intra-abdominal fat accumulation, and hypertension induced by sucrose diet in male rats

Sucrose-fed rats (1) had higher intra-abdominal fat mass and plasma non-esterified fatty acids and lower testosterone levels, (2) were hypertensive, and (3) had lower plasma NO metabolites than controls. The lack of testosterone by castration of sucrose-fed rats decreased high blood pressure and circulating non-esterified fatty acids and increased NO metabolites. The administration of testosterone to castrated sucrose-fed rats restored hypertension, fat accumulation, and high-circulating non-esterified fatty acids, and lowered NO metabolite levels whereas estradiol treatment did not significantly affect these variables in castrated animals. This study proposes that the low levels of testosterone found in sucrose-fed rats are sufficient to maintain central obesity and increased circulating non-esterified fatty acids, which contribute to the development of hypertension in sucrose-fed rats by modulating the biosynthesis of NO.     

Strength-interval relation in the human ventricle: Effect of procainamide

The effects of procainamide on strength-interval relations were evaluated in 18 patients. At plasma concentrations of 4.3 to 13.6 μg/ml procainamide had minimal effects on threshold current in late diastole, but in early diastole it shifted the strength-interval curve to the right. The basic strength-interval relation (that is, decreasing refractory period as current is increased) was not altered. The control refractory period decreased by a mean of 44 ms as the current was increased from threshold to 10 mA, whereas a mean decrease of 42 ms was observed after procainamide. However, the steep portion of the strength-Interval curve (absolute refractory period) was shifted to longer coupling intervals by a mean value of 24 ms. These findings suggest that procainamide may primarily affect active membrane properties, but exert little net effect on passive membrane properties late in diastole.     

Thyrotropin-releasing hormone (TRH)-Gly conversion to TRH in rat ventral prostate is inhibited by castration and aging

TRH levels in rat prostate are very high in the 2-month-old rat and decline at least 90% during the next 2 yr. This decline in prostatic TRH levels with aging may be a significant factor in benign prostatic hypertrophy in man and other animals. Because prostatic TRH correlates positively with serum testosterone and negatively with serum thyroid hormone levels, we have examined the possibility that the age-related decline in prostatic TRH is hormonally regulated. TRH and a TRH precursor peptide, TRH-Gly (pGlu-His-Pro-Gly), were measured in ventral prostates from 2-, 5-, and 18-month-old Fisher 344 male rats using a combination of HPLC and specific RIAs for TRH and TRH-Gly. Similar measurements were made in a group of 2-month-old Sprague-Dawley rats which were castrated, sham castrated, or left untreated for 3 or 7 days before death. Aging and castration resulted in a significant decrease in the absolute TRH concentration as well as the TRH/TRH-Gly ratio, but no significant change was observed in TRH-Gly levels. The serum testosterone concentration did not change with aging, but serum T4 levels fell significantly. Because testosterone levels do not change during the first 18 months of life in most rat strains, and hypothyroidism in young animals is associated with a significant increase in prostate TRH and TRH-Gly levels, we conclude that the aging-related decline in prostate TRH biosynthesis is not the result of a hypogonadal state.     

Effects of castration and testosterone replacement on peritoneal histamine concentration and lung histamine concentration in pubertal male rats

Mast cells, which are the main source of histamine, are significantly affected by sex steroids. The present study was undertaken to determine the effects of bilateral castration and testosterone replacement on peritoneal histamine concentration and lung histamine concentration in pubertal male rats (Wistar strain). Three groups of animals were used in this study: (1) untreated castrated animals, (2) castrated animals subjected to androgen replacement by injection of propionate of testosterone, and (3) intact males as a control group. Castration alone produced a dramatic reduction in peritoneal histamine concentration. In addition, androgen replacement was effective in restoring the histamine concentration to the normal value detected in the control males (P<0.05, Kruskal-Wallis test). On the other hand, there was no significant variation in the lung histamine concentration between control males, untreated castrated males and castrated males that received androgen replacement (P<0.05, Kruskal-Wallis test). These results demonstrate for the first time that castration markedly reduces the peritoneum histamine concentration in pubertal male rats, and testosterone replacement prevents the decrease. Further, these procedures do not affect lung histamine concentration, demonstrating that mast cells from different tissues may respond differently to the same biological factors.     

A transplantable rat Leydig cell tumour. 6. Effect of castration and hypophysectomy on tumour growth, morphology and plasma levels of pituitary hormones and testosterone

Growth rate and morphology were studied in a transplantable rat Leydig cell tumour (H-540) grown in intact, castrated and hypophysectomized rats. The plasma levels of pituitary hormones and testosterone were measured in the same rats. The results can be summarized as follows: 1. The growth curves of tumours in intact and castrated rats were S-shaped and very similar during the observation period of three weeks. 2. In hypophysectomized rats, the onset and progression of tumour growth were delayed, compared with intact and castrated rats. 3. The thymidine labelling index as well as the size of the S and G2 phase compartments were decreased in tumours greater than 10 g compared with smaller tumours and tumours grown in hypophysectomized rats. 4. Testosterone concentrations in plasma correlate well with increasing tumour weight up to approximately 10-15 g in intact and castrated rats. 5. Plasma testosterone levels in tumour-bearing hypophysectomized rats were 7-fold higher than those of corresponding intact and castrated rats. 6. In castrated rats, suppression of LH production occurs by very small tumours (less than 2 g), whereas FSH levels show a gradual decrease with increasing tumour size. PRL production was independent of castration, tumour weight, and testosterone levels. 7. In spite of no major differences in cell morphology, the morphometric analysis revealed a reduction in tumour cell size and nuclear size in hypophysectomized rats compared with intact and castrated rats. It is concluded that pituitary hormones stimulate tumour growth, but surprisingly appear to reduce the secretion of testosterone from these tumours.     

Effect of testosterone on the rate of myofibrillar protein breakdown in castrated and adrenalectomized male rats measured by the urinary excretion of 3-methylhistidine

Urinary output in N^τ-methylhistidine (3-MeHis) was used to evaluate changes in myofibrillar protein breakdown rate in the skeletal muscles of castrated and adrenalectomized-castrated young male rats, and the responses of breakdown to testosterone and corticosterone replacement. The castrated rats grew less well than intact control rats and excreted significantly less 3-MeHis. Administration of low and high doses of testosterone restored the weight of the levator ani of the castrated animals but failed to affect growth rate or 3-MeHis output. Although this might suggest that testosterone has an indirect effect on muscle turnover through changes in growth rate, this parallelism was not confirmed by studies on adrenalectomized-castrated rats. Adrenalectomy of castrated rats caused a further reduction in growth rate and in output of 3-MeHis, but administration of testosterone now reduced 3-MeHis output still further while stimulating growth. Treatment of the adrenalectomized-castrated rats with low doses of corticosterone increased growth modestly, while depressing 3-MeHis output, and again output of this metabolite was further reduced when testosterone was added to the treatment, although growth rate was unaffected. Finally, large doses of testosterone given to adrenalectomized-castrated rats receiving excessive amounts of corticosterone did not prevent the growth failure or the increased output of 3-MeHis due to the corticosteroid, though it appeared to reduce the magnitude of the response to corticosterone alone. It is concluded that the effects of testosterone on growth and on 3-MeHis output are not necessarily associated and that the functional status of the adrenal cortex modifies the response of myofibrillar breakdown rate to testosterone treatment.     

Subthreshold conditioning stimuli prolong human ventricular refractoriness

This study tested whether a subthreshold stimulus (Sc) inserted before a premature stimulus prolonged the right ventricular effective refractory period in humans, and whether the degree of effective refractory period lengthening was influenced by heart rate, Sc current intensity or Sc pulse duration. Sc at current intensity 10 mA and pulse width 2 ms prolonged mean effective refractory period from 255 ms to 277 ms (p less than 0.001, n = 20). The increase in effective refractory period was similar in 6 patients studied at pacing cycle lengths 600 (259 to 289 ms) and 400 ms (236 to 258 ms). When Sc current intensities were varied at 2, 5 or 10 mA at a constant pulse duration of 100 ms the effective refractory period progressively prolonged by 6, 40 and 81 ms respectively (p less than 0.02, n = 6). The pulse duration of Sc at a constant current of 10 mA significantly influenced effective refractory period prolongation. With Sc pulse durations of 2, 10, and 100 ms the effective refractory period prolonged by 16, 33 and 66 ms respectively (p less than 0.01, n = 7). Thus, subthreshold impulses prolong the effective refractory period in human right ventricular myocardium. The prolongation of effective refractory period depended on Sc current intensity and pulse duration but was independent of heart rate at the cycle lengths tested. The use of subthreshold stimuli as antiarrhythmic therapy may be feasible in some patients.     

Diminished role of LHRH in the control of gonadotroph morphology and function in the long-term castrated male rat

It was found in previous studies that the neurotransmitter control of the secretion of LHRH and LH differs between long-term castrated and ovariectomized rats. One interpretation of these data was that there was a reduced 'positive drive' in the male, and the question was raised 'how do the gonadotrophs of long-term castrated rats maintain a high level of LH secretion?'. In the present series of experiments, evidence for a reduced dependence of the gonadotrophs upon LHRH stimulation is provided. Although sensitivity to native LHRH was not completely lost in long-term castrated rats, two potent LHRH antagonists (D-pyroglu1,D-Phe2,D-Trp3,6)-LHRH and (N-acetyl-3,4-dehydro-Pro,p-fluoro-D-Phe2,D-Trp3,6)-LHRH, were found to inhibit LH secretion in short-term castrated and long-term ovariectomized rats, but not in long-term castrated rats. Neither blockade of axonal transport with colchicine nor immunoneutralization of LHRH with an antiserum against LHRH (both administered 48 h before blood sampling) produced reductions in serum concentrations of LH in long-term castrated rats, although these treatments significantly suppressed LH levels in short-term castrated animals. Chronic (6-day) infusions of the second LHRH antagonist (up to 450 micrograms/day) neither reduced LH secretion nor altered the morphology of the 'castration cells' in the pituitaries of long-term castrated rats. Chronic treatment with testosterone (15 days), however, reversed these parameters to some extent, and when the testosterone treatment was coupled with chronic infusions of the LHRH antagonist, significantly lower serum levels of LH and reductions in the size of the castration cells were observed. These data thus indicate that castration cells may function autonomously, without the need for LHRH, and that testosterone in some way restores the dependency on LHRH and/or the responsiveness to LHRH of these cells.     

Contraction-excitation feedback in the atria: a cause of changes in refractoriness

The purpose of this study was to investigate the immediate effects of an increase in atrial pressure on atrial refractoriness by determining the relation between the atrial pressure and effective refractory period of the atrium. In 21 open chest anesthetized dogs, after the blocking of atrioventricular (AV) conduction by formalin injection, the left atrium and left ventricle were paced sequentially at a fixed cycle length of 300 ms. The AV interval was varied from 0 to 280 ms in 20 ms steps during the recording of aortic and left atrial pressures and refractory period of the left atrium. Mean left atrial pressure was lowest (8.0 +/- 0.4 mm Hg, all values mean +/- SEM) at an AV interval of 47 +/- 3 ms, when refractory period was 135.5 +/- 2.6 ms. Mean left atrial pressure was highest (13.3 +/- 0.5 mm Hg) at an AV interval of 147 +/- 5 ms, when refractory period was 137.9 +/- 2.4 ms (p less than 0.01). Left atrial diameter measured by echocardiography increased from 33.7 +/- 1.8 mm at an AV interval of 47 ms to 37.8 +/- 1.8 mm (p less than 0.01, n = 10) at an AV interval of 147 ms, and mean aortic pressure decreased from 109 +/- 4 to 101 +/- 4 mm Hg. After surgical decentralization of vagal and sympathetic innervation to eliminate baroreflex influence on refractoriness, left atrial refractory period prolonged from 141.6 +/- 3.4 to 145.4 +/- 3.4 ms (p less than 0.01) when mean left atrial pressure increased from 9.5 +/- 0.4 to 15.2 +/- 0.6 mm Hg. A similar relation was noted between right atrial pressure and right atrial refractory period (n = 10) and between left atrial pressure and refractory period of the interatrial septum (n = 12). In six chronically instrumented conscious dogs, left atrial refractory period prolonged from 116.3 +/- 2.3 to 124.2 +/- 1.7 ms (p less than 0.01) when mean left atrial pressure increased from 4.0 +/- 0.8 to 9.0 +/- 0.3 mm Hg. Therefore, an increase in atrial pressure lengthens refractory period of both atria and the interatrial septum in anesthetized and conscious dogs.     

Effect of Sex Hormones on Non-Esterified Fatty Acids,Intra-Abdominal Fat Accumulation,and Hypertension Induced by Sucrose Diet in Male Rats

Sucrose-fed rats () had higher intra-abdominal fat mass and plasma non-esterified fatty acids and lower testosterone levels, () were hypertensive, and () had lower plasma NO metabolites than controls. The lack of testosterone by castration of sucrose-fed rats decreased high blood pressure and circulating non-esterified fatty acids and increased NO metabolites. The administration of testosterone to castrated sucrose-fed rats restored hypertension, fat accumulation, and high-circulating non-esterified fatty acids, and lowered NO metabolite levels whereas estradiol treatment did not significantly affect these variables in castrated animals. This study proposes that the low levels of testosterone found in sucrose-fed rats are sufficient to maintain central obesity and increased circulating non-esterified fatty acids, which contribute to the development of hypertension in sucrose-fed rats by modulating the biosynthesis of NO.