Effect of vagotomy on postcastration gonadotropin secretion in male rats

The postcastration increase in gonadotropins was studied in intact and vagotomized male rats. Rats underwent vagotomy or sham surgery immediately prior to castration. In the first experiment, rats were bled before castration and at 1, 2, 4, and 7 days after castration. Serum LH and FSH were significantly lower in vagotomized rats 1 day after castration. On days 2, 4, and 7 postcastration, serum gonadotropin levels were generally not different among experimental groups. In a second experiment, rats were decapitated at 12 or 24 hr after surgery and castration. Trunk blood was collected for assay of LH. Vagotomy had no effect on LH levels at 12 hr postcastration, but, at 24 hr postcastration, vagotomized rats had significantly lower serum LH than did sham-operated rats. These experiments indicate that vagotomy has a transient suppressive effect on gonadotropin release following castration. Such observations support the hypothesis that the vagus nerve may play a modulatory role in gonadotropin secretion.     

Effects of serotonin and stress on the state of the gastric mucosa in rats with the intact and transsected vagus nerve

In experiments on vagotomized and intact rats with the use of two models of experimental gastric ulceration (injection of serotonin and stress) it was demonstrated that the inhibitory action of vagotomy on haemorrhagic gastric effectiveness was more pronounced in stress than after serotonin application. Vagotomy decreased stress-induced erosive lesions but increased serotonin-induced erosions that may be a result of the increase of gastric tissue sensitivity to this amine which developed simultaneously with significant decrease of its level in gastric wall after vagotomy. Serotonin-antagonist peritol decreased stress-induced gastric disturbances in vagotomized rats more significantly than in intact rats; this suggested the great role of serotonin in anti-ulcerogenic effect of vagotomy.     

Effect of vagotomy on the morphological and functional state of the rat adrenal medulla

After bilateral subphrenic vagotomy in male rats (in 7 and 45 days) there was revealed a sharp dilatation of the venous sinusoids, diminution of the chromaffin tissues area, and a more intensive chromaffin reaction in the adrenal medulla. Vagotomy resulted in a marked alteration of the ultrastructural organization of the secretory cells and the endothelium. Glucose administration to vagotomized animals caused only insignificant variations in adrenaline content in the chromaffin cells. Thus, vagotomy resulted in reduction of the functional activity of the adrenal medulla secretory cells.     

The effect of natural and synthetic antioxidants on the profile of the parietal pH of the digestive tract in rats under normal and pathologic conditions

The effect of natural (alpha-tocopherol) and synthetic (Dibunol and VN-3) antioxidants on H+ ion concentration in paramucous layer (PpH) of gut, duodenum, caecum, jejunum, and rectum in normal and vagotomized rats has been estimated 7, 14, and 30 days after introduction of the drugs. Vagotomy leads to transformation of the PpH shape of digestive tract. The effect is most pronounced at 7 days and reveals itself as an increase in PpH in gut, the decrease in PpH in duodenum and caecum. Introduction of E vitamin for 7 days led to the decrease in gut PpH and the increase in duodenum PpH in both groups of animals. Dibunol and VN-3 did not exert significant influence on the PpH of digestive tract of normal and vagotomized rats. An inhibitory effect of VN-3 on gut contractile activity in both groups of animals has been observed.     

Effect of exogenous melatonin on neuroendocrine-reproductive function of middle-aged female rats

The possible role of melatonin in the regulation of the reproductive system of female rats during ageing was investigated in middle-aged female rats showing irregular duration of the oestrous cycle (n = 30). Blood samples were obtained by jugular venepuncture during the oestrous cycle in control rats. After this experiment was completed, the female rats were treated with melatonin for 2 months and blood samples were obtained at different stages of the oestrous cycle. Plasma LH, FSH and prolactin concentrations were significantly increased in the afternoon of the day of pro-oestrus after melatonin treatment compared with control rats. Moreover, FSH concentrations too were significantly increased on the morning of pro-oestrus and oestrus in melatonin treated rats compared with control rats. Similarly, oestradiol concentrations were significantly higher on the morning of pro-oestrus in melatonin treated rats compared with controls. Another group of rats showing irregular duration of the oestrous cycle was used to study the possible effect of melatonin treatment on the timing of pro-oestrous surges of LH and FSH. The results showed that LH and FSH peak values occurred at 5 h after melatonin treatment. Pituitary responsiveness to LHRH in a 90 min test was also studied in middle-aged rats showing irregular duration of the oestrous cycle that had been injected for 1 month with either melatonin or saline. Prolactin response was unaffected by exogenous melatonin, but a stimulatory effect of melatonin on LH and FSH pituitary responsiveness to LHRH was observed. The results indicate an improved function of the neuroendocrine-reproductive axis in middle-aged rats after melatonin treatment.     

Use of dibunol in pharmacological correction of post-vagotomy hypoxia of digestive organs in rats

1, 7, 14, 30 and 60 days after bilateral sub-diaphragmatic truncal vagotomy tension of oxygen (pO2) in liver, stomach and small intestine (jejunum) was determined. It was demonstrated that vagotomy leads to a decrease of pO2 in all investigated organs 1 day after the operation (such changes were observed in sham-operated rats) and 30 days, in jejunum--after 7 days, in liver--after 14 days, in stomach--after 60 days. Dibunol introduction in vagotomized rats during 29 days (starting from the second day after operation) results in pO2 normalization in all investigated organs.     

The effect of epostane (Win32739), an inhibitor of 3β-hydroxy steroid dehydrogenase,on luteal function and gonadotrophin secretion in cows

Six cows were injected i.m. with either 4 × 125 mg or 4 × 250 mg of the 3β-hydroxy steroid dehydrogenase inhibitor epostane (Win32729) at 12-h intervals during the luteal phase of the oestrous cycle. Four more cows received 1 × 1 g epostane i.m. In all cows there was a transient decrease in plasma progesterone concentrations beginning within 8 h of the first injection, the decrease being more rapid and greater in the group receiving 1 × 1 g epostane. However, progesterone concentrations did not reach basal values and no preovulatory LH or FSH surges occurred. Progesterone concentrations invariably returned to pre-injection values within a few days and the length of the oestrous cycle was not affected. During the treatment period there were significant negative correlations between mean plasma LH and progesterone concentrations.     

The protective effect of the vagus nerve in a murine model of chronic relapsing colitis

The vagus nerve inhibits the response to systemic administration of endotoxin, and we have recently extended this observation to show that the vagus attenuates acute experimental colitis in mice. The purpose of the present study was to determine whether there is a tonic counterinflammatory influence of the vagus on colitis maintained over several weeks. We assessed disease activity index, macroscopic and histological damage, myeloperoxidase (MPO) activity, and Th1 and Th2 cytokine profiles in chronic colitis induced by administration of dextran sodium sulfate (DSS) in drinking water for three cycles during 5 days with 11 days of rest between each cycle (DSS 3, 2, 2%) in healthy and vagotomized C57BL/6 mice and in mice deficient in macrophage-colony stimulating factor (M-CSF). A pyloroplasty was performed in vagotomized mice. Vagotomy accelerated the onset and the severity of inflammation during the first and second but not the third cycle. Although macroscopic scores were not significantly changed, histological scores as well as MPO activity and colonic tissue levels of IL-1alpha, TNF-alpha, IFN-gamma, and IL-18 but not IL-4 were significantly increased in vagotomized mice compared with sham-operated mice that received DSS. In control mice (without colitis), vagotomy per se did not affect any inflammatory marker. Vagotomy had no effect on the colitis in M-CSF-derived macrophage-deficient mice. These results indicate that the vagus protects against acute relapses on a background of chronic inflammation. Identification of the molecular mechanisms underlying the protective role of parasympathetic nerves opens a new therapeutic avenue for the treatment of acute relapses of chronic inflammatory bowel disease.     

Neonatal castration of male and female rats affects luteinizing hormone responses to estrogen during adulthood

We examined the positive and negative feedback effects of estradiol (E2) on luteinizing hormone (LH) and prolactin (Prl) secretion in adult male and female rats which were gonadectomized within 24 h after birth (long-term castrates) and compared these responses to those elicited by E2 in short-term castrated (7 days) adult males and females. The high serum E2 did not reduce the elevated serum LH concentrations in long-term castrates until 4 days of treatment. Also, only after negative feedback was established were the positive feedback actions of E2 observed. In contrast, Prl surges were observed after 2 days of E2, and baseline Prl serum levels were elevated by Day 3 of E2 in long-term castrated male and female rats. Some long-term castrates lacked both LH and Prl surges, and E2 was ineffective in altering basal gonadotropin secretion in these animals. Short-term castrated males had elevated serum Prl levels but no Prl surges. Seemingly, when the hypothalamus is deprived of estrogen or androgen from birth to adulthood, an equal percentage of males and females become refractory to the positive feedback effects of estrogen during adulthood. Thus, it is difficult to separate castration effects from those which may be produced by the endogenous androgen secreted during the first 26 h of life.     

Inspiratory muscle activity during unloaded and obstructed rebreathing in dogs

Moving-average electromyogram (EMG) of the diaphragm (DI), scalenes, and cranial and caudal parasternals was assessed in anesthetized, supine, and head-up dogs during rebreathing. The shape of EMG trajectory was similar for all muscles and conditions; activation of different muscles could be thus compared on the basis of changes in peak activity. In intact dogs changes in peak activity were greater for the scalenes and cranial parasternals than for the caudal parasternals and greater for the inspiratory thoracic muscles (ITM) than for the DI. Posture, vagotomy, and cordotomy at C7-T1 did not affect the rate of rise of DI activity. The relations between peak activity of ITM did not change because of posture, vagotomy, and phrenicotomy. Vagotomy selectively depressed the rate of rise of ITM activity, but relative changes in peak ITM activity for a given change in peak DI activity were independent of intact vagi. Differences in the pattern of activation between inspiratory muscles with rebreathing are largely independent of proprioceptive inputs and likely reflect properties of central control mechanisms. However, airway occlusion at end expiration caused a reflex fall of DI activity and reflex increase of ITM activity in intact and vagotomized dogs. Cordotomy at C7-T1 did not change DI response, whereas reduction of ITM activity occurred after phrenicotomy, indicating that both facilitatory and inhibitory segmental inputs are involved in ITM response to loading.     

Diurnal rhythm of changes in the DNA-synthesizing cell count and the mitotic activity of the cells of jejunal epithelium under conditions of subdiaphragmatic vagotomy

Bilateral subdiaphragmatic vagotomy in rats 7 days after surgery results in increasing proliferative activity of the jejunum epithelium not changing circadian rhythm of the mitotic process. Vagotomy induces changes in the diurnal rhythm structure of DNA-synthesis in the jejunum epithelial cells, i.e. monoapical rhythm in the norm becomes biapical.     

Hormone responses to low-dose GnRH treatment in post-partum beef cows

Acyclic beef cows received 1.0, 2.5 or 5.0 micrograms GnRH/2 h for 48 h as 24 X 2 h repeated i.v. injections or by continuous i.v. infusion. Preovulatory-type LH surges were detected in 9/18 injected and 8/15 infused cows and occurred 30.6 +/- 5.1 h and 3.3 +/- 0.7 h after the start of treatment respectively. Cows receiving the lowest infusion dose did not exhibit gonadotrophin surges. The LH response to individual injections increased with dose but the proportion of injected cows showing preovulatory-type surges at each dose level did not change. A total of 20 cows (10 injected and 10 infused) showed evidence of luteal activity within 7 days of the end of GnRH treatment, although this was transitory in most animals. Cows which exhibited preovulatory-type LH surges in response to treatment had significantly higher plasma oestradiol-17 beta concentrations and lower FSH concentrations before treatment than those which did not. The results suggest that the LH response to GnRH treatment is dependent on follicular status in the immediate pretreatment period.     

Effect of synthetic phenol antioxidants on the parietal pH value of the gastrointestinal tract in intact and vagotomized rats

The influence of synthetic phenol antioxidants dibunol and BH-3 on the value of parietal pH has been studied in the stomach, duodenum, jejunum, ileum, caecum and rectum of intact and vagotomized rats 1, 7, 14, 30 and 60 days after treatment. It was shown that vagotomy leads to an increase in the stomach pH and to a decrease in pH in other parts of the gastrointestinal tract. Maximum BH-3 doses lead to pH increase in the stomach of intact rats. Chronic administration of therapeutic drug doses does not change pH value in control and vagotomized animals.     

Loss of luteinizing hormone surges induced by chronic estradiol is associated with decreased activation of gonadotropin-releasing hormone neurons

Chronic exposure of young ovariectomized rats to elevated circulating estradiol causes loss of steroid-induced LH surges. Such LH surges are associated with cFos-induced activation of GnRH neurons; therefore, we hypothesized that chronic estradiol treatment abolishes LH surges by decreasing activation of GnRH neurons. Regularly cycling rats were ovariectomized and immediately received an estradiol implant or remained untreated. Three days or 2 or 4 wk later, the estradiol-treated rats received vehicle or progesterone at 1200 h, and 7 hourly blood samples were collected for RIA of LH. Thereafter, all rats were perfused, and the brains were examined for immunocytochemical localization of cFos and GnRH. The GnRH neurons from untreated ovariectomized rats rarely expressed cFos. As reported, LH surges induced by 3 days of estradiol treatment were associated with a 30% increase in cFos-containing GnRH neurons, and progesterone enhanced both the amplitude of LH surges and the proportion of cFos-immunopositive GnRH neurons. As hypothesized, the abolition of LH surges caused by 2 or more weeks of estradiol was paralleled by a reduction in the percentage of cFos-containing GnRH neurons, and this effect was delayed by progesterone. These results suggest that chronic estradiol abolishes steroid-induced LH surges in part by inactivating GnRH neurons.     

Effect of abdominal vagotomy of the pregnant rat on LH and progesterone concentrations and fetal resorption

Abdominal vagotomy on Day 8 of pregnancy in rats decreased the number of live fetuses at Day 16 and increased the number of resorbing fetuses. The activity of delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the corpus luteum and interstitial gland, LH and progesterone values in plasma and progesterone values in ovarian tissue were all lower in vagotomized rats than in sham-operated controls. Ovarian PGF levels were not affected. We suggest that these effects were caused by a direct effect of vagotomy on LH secretion which in turn lowers 3beta-HSD activity and progesterone levels in ovarian tissue and plasma, leading to fetal resorption.     

Effects of estradiol on the prolactin surges and the feedback mechanisms of gonadotropins in pseudopregnant rats

The influences of estradiol on the prolactin (PRL) surges and on the secretion of gonadotropins (LH and FSH) were investigated in the pseudopregnancy (PSP) of acutely ovariectomized rats. The four following experimental groups were prepared: 1) intact PSP as a control, 2) ovariectomy was performed on day 0 of PSP (OVX), 3) a Silastic tube containing estradiol was implanted for day 1-4 into the OVX rats (OVX-E 1-4), and 4) the Silastic tube was implanted for day 5-8 by the same manner into the OVX rats (OVX-E 5-8). In the OVX group nocturnal (N) PRL surges were observed at 0500 h on days 4, 8 and 12 examined, and increased secretions of LH and FSH were noted. In the OVX-E 1-4 group, the N PRL surge was suppressed on day 4, and the suppressed N PRL surge did not occur on day 8, after the removal of the implanted tubes. Diurnal (D) PRL surges with LH surges were observed at 1700 h on day 4 in these rats. Similarly, more remarkable results were obtained on days 8 and 12 in the OVX-E 5-8 group than in the OVX-E 1-4.(ABSTRACT TRUNCATED AT 250 WORDS)     

Involvement of the neurointermediate lobe of the pituitary gland in the secretion of prolactin and luteinizing hormone in the rat

The relationship between prolactin (PRL) secretion and the neurointermediate lobe (NIL) of the pituitary gland was investigated. Plasma PRL concentrations in rats bearing anterior pituitaries autografted with or without the NIL to the renal capsule were elevated to equal extents at 1 through 6 weeks after surgery (p > 0.10). PRL levels in ovariectomized rats in which the NIL had been removed surgically (NIL-X) or only visualized (NIL-C) were 3–7 ng/ml 4, 7, and 28 days after surgery (p > 0.10); however, they were slightly higher in NIL-X $\text{vs.}$ NIL-C rats 14 days after surgery (p < 0.05). Plasma luteinizing hormone (LH) concentrations in NIL-C rats increased by 36% from 2 to 4 weeks after surgery (p < 0.05); this increase was not detected in NIL-X rats. PRL and LH surges were induced by estradiol implants in ovariectomized NIL-X and NIL-C rats; the profiles of the PRL surges were superimposable, although the magnitude of the LH surge was only 50% that in NIL-C rats (p < 0.05). These results cast doubt on the importance of the NIL in the regulation of PRL secretion either $\text{via}$ secreting hypophysiotropic hormones or $\text{via}$ conducting anterior pituitary hormones directly to the median eminence. However, the NIL may have a physiologically important role in the regulation of LH secretion.     

Species differences in circulatory responses to nasopharyngeal perfusion with smoke

Cardiovascular changes were observed in five species of laboratory mammals during upper airway perfusion with cigarette smoke. Apnoea occurred, both before and after vagotomy, in all species. Blood pressure always went up in rabbits, rats and hamsters but was not much affected in cats and guinea-pigs. Before vagotomy heart rate fell in rabbits and rats, rose in hamsters but did not change in cats and guinea-pigs. Vagotomy affected heart rate changes only in rabbits and rats. Results demonstrate markedly different autonomic responses in different species.     

The effect of vagotomy on the satiety effects of neuropeptides and naloxone

As abdominal vagotomy blocks the satiety effect of cholecystokinin-octapeptide, we felt it would be worthwhile to examine whether the satiety effect of any of the other putative satiety neuropeptides was mediated through the vagus. We confirmed that the satiety effect of peripherally administered cholecystokinin (10 micrograms/kg) was mediated through the vagus. In addition, the satiety effect of peripherally administered TRH (8 mg/kg) also was not present in vagotomized animals. Vagotomy had no effect on the satiety effects of peripherally administered bombesin, calcitonin and naloxone. Nor did vagotomy alter the satiety effect produced by central administration of bombesin, TRH, calcitonin nor naloxone.     

Chronic elevation of estradiol in young ovariectomized rats causes aging-like loss of steroid-induced luteinizing hormone surges

This study was designed to test the hypothesis that the loss of LH surges in response to the stimulatory actions of estradiol and progesterone in middle-aged, persistent-estrous (PE) rats may be caused by chronic elevations in circulating estradiol. Five groups of regularly cycling young rats received an s.c. estradiol implant immediately after ovariectomy (Day 0). For determination of LH surges, blood samples were collected hourly between 1200-1900 h from each of the five groups at one of the following times: 3 days, or 1, 2, 4, or 8 wk later. On the next day, either progesterone (0.5 mg/100 g BW) or corn oil was injected s.c. at 1200 h, and samples were obtained as before. Incidence and amplitude of estradiol-induced LH surges decreased during the first 2 wk of estradiol treatment, after which no surges occurred. Progesterone enhanced the incidence and amplitude of estradiol-induced LH surges thus delaying their disappearance. These results support our hypothesis and demonstrate that the stimulatory actions of estradiol and progesterone on the LH surge sequentially diminish with time after exposure to estradiol in young rats. Thus, young rats chronically treated with estradiol may be a useful model for studying the mechanisms whereby LH surges are abolished in middle age during the hyperestrogenic state of PE.