Delta-sleep-inducing peptide (DSIP) inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro

Delta-sleep-inducing peptide (DSIP, 10(-9) - 10(-7) M) significantly inhibited the CRF-induced ACTH release from rat anterior pituitary quarters in vitro. 10(-8) M DSIP showed the most prominent inhibition. DSIP (10(-8) M) also inhibited the CRF-activated cAMP levels in anterior pituitary tissue. DSIP did not influence basal ACTH or cAMP levels. Prostaglandin E2 (PGE2)-release from anterior pituitary quarters was not changed by DSIP. From these results, we conclude that DSIP inhibits CRF-induced ACTH release at the pituitary level through the inhibition of the cAMP system in corticotrophs. The involvement of PGE2 in this phenomenon is unlikely.     

Prepubertal changes in the hypothalamic-pituitary axis of Holstein bulls

We investigated the nature and sites of changes in the hypothalamic-pituitary axis associated with the onset of high-frequency, high-amplitude discharges of luteinizing hormone (LH) in young bulls during the transition from the infantile to the prepubertal phase of development. Blood serum and neuroendocrine tissues from bulls killed at 1, 6, 10, 14, or 18 wk of age were evaluated. Concentrations of LH in serum from bulls 1 or 6 wk old averaged less than 0.25 ng/ml and only one episodic discharge of LH was detected for 10 bulls. At 10, 14, or 18 wk, 14 of 15 bulls had episodic discharges of LH. Concentrations of testosterone in serum were progressively higher at 10, 14, and 18 wk, but the concentration of estradiol was maximal at 6 wk. The concentrations of gonadotropin-releasing hormone (GnRH) in the anterior hypothalamus, posterior hypothalamus, or median eminence were not influenced by age. However, concentration of GnRH receptors in the anterior pituitary gland increased 314% between 6 and 10 wk and the concentration of LH increased 67%. Between 6 and 10 wk, concentrations of estradiol receptors in the anterior and posterior hypothalamus declined by 68% and 46%, but the concentration of estradiol receptors in the anterior pituitary gland increased by 103%. For most characteristics, there was no major change between 10 and 18 wk. We postulate that between 6 and 10 wk of age, there is 1) removal of an estradiol-mediated block of GnRH secretion and 2) an estradiol-mediated, and possibly GnRH-mediated, increase in pituitary GnRH receptors. Together, these changes result in greatly increased stimulation of the anterior pituitary gland by GnRH between 6 and 10 wk of age and stimulation of the discharges of LH characteristic of bulls in the early prepubertal phase of development.     

In vivo and in vitro effects of LH-RH on cAMP content of anterior pituitary in rats.

Changes in the cAMP content of anterior pituitary of male rats were studied after in vivo administration of LH-RH or in vitro incubation in the presence of LH-RH. Although a significant rise was observed 5 min after in vivo injection of LH-RH, the cAMP level increased after only a two-hour lag period in vitro. Maximum level was reached in vivo with 1 microgram LH-RH/100 g b.w., but there was no maximal production in vitro even in the presence of 5 x 10(-6) M LH-RH. A summary of the available observations on the effect of LH-RH on pituitary cAMP level is given in the present paper.     

Effect of ethanol on androgen receptors in the anterior pituitary, hypothalamus and brain cortex in rats

The purpose of this study was to investigate ethanol-induced changes in androgen receptor sites in the anterior pituitary, hypothalamus, and brain cortex. Young adult male King-Holtzman rats were fed for 5 months a nutritionally complete liquid diet, with ethanol or isocaloric sucrose constituting 36% of the total calories. Androgen receptor sites were measured by sucrose density gradient and charcoal assay using tritiated dihydrotestosterone (DHT). Scatchard plot analysis of the data revealed that apparent dissociation constants of DHT-receptor complex for the anterior pituitary, hypothalamus, and brain cortex from alcohol-fed animals were estimated to be 0.7 +/- 0.13, 0.6 +/- 0.16 and 0.9 +/- 0.15 nM, respectively. These values are identical to those of their isocaloric controls. The concentrations of cytosol androgen receptors of the pituitary, hypothalamus, and brain cortex from alcohol-fed rats were 8.0 +/- 1.2, 6.2 +/- 1.0 and 4.9 +/- 0.7 fmol/mg protein, respectively. This represents about a 34, 24, and 22% reduction when compared to the values of the isocaloric control animals. In contrast to control rats, neither castration nor androgen or LHRH replacement to castrated alcohol-fed rats altered an alcohol-induced reduction of androgen receptor contents. Serum LH and testosterone levels were significantly decreased in alcohol-fed rats but these hormone levels were increased by administration of LHRH or norepinephrine. Such reduction of androgen receptors, serum LH and testosterone, but enhancement of these hormone levels by treatment with neurohormone and neurotransmitter in these animals suggests that ethanol exerts an adverse effect on the hypothalamic-pituitary unit and the neurotransmitter-hypothalamic hormone relationship, resulting in impairment of the androgen-induced sexual events and a suppression of the pituitary gonadotropin secretion.     

Changes in the level of epidermal G2-chalone and mitotic activity in the rat vaginal epithelium]

The content of tissue-specific inhibitor of mitosis in epidermal epithelium (G2-chalone) was estimated by a single radial immunodiffusion test in the rat vagina during various stages of the estrous cycle. The level of chalone was found to correlate with the mitotic index (MI) of vaginal epithelium. The lowest level of G2-chalone is detected in proestrus and the highest one in estrus. The level of G2-chalone in vaginal epithelium was shown to be significantly decreased in aging rats (14--16 month-old) with regular cycles as compared to that in young normal cycle rats (3--4 month-old). The single injection of estradiol benzoate (1 microgram/100 g) into ovariectomized rats led to an increase in the MI following 18 hours. The increased MI is preceeded by a substantial drop of the G2-chalone level 12 hours after estrogen injection.     

Increase of thyrotropin response to thyrotropin-releasing hormone (TRH) and TRH release in rats during pregnancy

Regulation of thyrotropin (TSH) release by thyrotropin releasing hormone (TRH) in the anterior pituitary gland (AP) of pregnant rats was studied. The pregnant (day 7, 14, and 21) and diestrous rats were decapitated. AP was divided into 2 halves, and then incubated with Locke's solution at 37 degrees C for 30 min following a preincubation. After replacing with media, APs were incubated with Locke's solution containing 0, or 10 nM TRH for 30 min. Both basal and TRH-stimulated media were collected at the end of incubation. Medial basal hypothalamus (MBH) was incubated with Locke's medium at 37 degrees C for 30 min. Concentrations of TSH in medium and plasma samples as well as the cyclic 3':5' adenosine monophosphate (cAMP) content in APs and the levels of TRH in MBH medium were measured by radioimmunoassay. The levels of plasma TSH were higher in pregnant rats of day 21 than in diestrous rats. The spontaneous release of TSH in vitro was unaltered by pregnancy. TRH increased the release of TSH by AP, which was higher in pregnant than in diestrous rats. Maternal serum concentration of total T3 was decreased during the pregnancy. The basal release of hypothalamic TRH in vitro was greater in late pregnant rats than in diestrous rats. After TRH stimulation, the increase of the content of pituitary cAMP was greater in late pregnant rats than in diestrus animals. These results suggest that the greater secretion of TSH in pregnant rats is in part due to an increase of spontaneous release of TRH by MBH and a decrease of plasma thyroid hormones. Moreover, the higher level of plasma TSH in rats during late pregnancy is associated with the greater response of pituitary cAMP and TSH to TRH.     

Changes in the hypothalamic-hypophyseal axis of mares in relation to the winter solstice.

In mares, the amount of gonadotrophin-releasing hormone (GnRH) is low in the hypothalamus during seasonal anoestrus, but by early spring, concentrations of GnRH are high. The timing of this response was characterized more precisely by determining concentrations of GnRH in hypothalamic tissue collected immediately before and at various times after the winter solstice (22 December 1986). Ovaries, pituitary gland, hypothalamus and a blood sample were collected from six groups of mares (6-12 mares per group) at death, 1 week before day of the winter solstice and 1, 2, 3 and 12 weeks afterwards. No significant changes in weight of the anterior pituitary gland or concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were observed in the anterior pituitary gland (P > 0.1). Mean diameter of the largest follicle, number of follicles > or = 20 mm in diameter and concentrations of LH and FSH in serum remained unchanged for weeks -1 to +3 (P < 0.05), then increased significantly by week 12 (P < 0.001). Content and concentration of GnRH in the median eminence was low at -1 week, increased gradually (P < 0.05) to a maximum by +1 week, then decreased gradually (P < 0.05) to low values at 12 weeks. Means (+/- SEM) for -1, +1 and +12 weeks were 33.5 +/- 5.5, 117.7 +/- 18.6 and 29.8 +/- 3.7 ng GnRH, respectively. Mean content of GnRH in the preoptic area of the hypothalamus showed a reciprocal pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunoreactive LHRH in chronic starved rats

The effects of chronic starvation (1/4 of ad libitum food intake) for 21 or 30 days were studied on the hypothalamic and serum concentrations of LHRH, the pituitary and serum concentrations of LH, and the weights of the anterior pituitary, ovary and uterus in adult female Wistar rats (chronic starved group, CSG). Control female rats were fed ad lib. for the same periods (control group, CG). On day 22 or 31, half of the rats of each group were weighed and sacrificed by decapitation. Since there were no difference on above parameters between the experiments on 22nd and 31st day, the results were combined for each parameters. At the time of sacrifice, the body weight of CSG was on the average 44% lower than that of CG rats, and also marked reduction in anterior pituitary (44%), ovarian (61%) and uterine weights (69%) was observed. Serum LH concentrations (mean +/- SE; 5.67 +/- 0.67 versus 33.30 +/- 6.00 ng/ml, P less than 0.001) and pituitary LH content (286.7 +/- 19.4 vs 451.0 +/- 32.8 micrograms, P less than 0.001) were significantly decreased in CSG than in CG rats. However, pituitary LH concentration was not reduced because of the proportional reduction to the pituitary weight of CSG rats. Hypothalamic immunoreactive LHRH (IR-LHRH) content in CSG showed a significant increase as compared to CG rats (5.77 +/- 0.52 vs 4.41 +/- 0.27 ng/hypothalamic extract, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.

A local renin-angiotensin system (RAS) that may be involved in their regulatory functions has been identified in hypothalamus and pituitary. Altered thyroid status induces modifications in the secretory function of hypothalamus and pituitary. However, few studies have analyzed the role of the RAS in hypothalamus and, to our knowledge, there is no data on the pituitary RAS during thyroid dysfunction. In the present study, angiotensinase activities (glutamyl, aspartyl and alanyl aminopeptidase: GluAP, AspAP and AlaAP, respectively) were studied in hypothalamus and in the anterior and posterior lobes of pituitary of euthyroid, hypothyroid and hyperthyroid adult male rats. In the anterior pituitary, compared with euthyroid and hyperthyroid rats, hypothyroid animals showed a highly significant increase of GluAP and AspAP activities; the percentage increase in GluAP was markedly higher than the percentage increase in AspAP. This suggests an increased metabolism of angiotensin (Ang) I and Ang II to des-Asp 1-Ang I and Ang III, respectively. We also observed an increase of Ang III-degrading activity (AlaAP) in the hypothalamus of hyperthyroid rats in soluble fraction. Increased Ang I and Ang II metabolism in the anterior pituitary of hypothyroid rats and increased metabolism of Ang III in the hypothalamus of hyperthyroid animals may be related to alterations in the secretory function of hypothalamus and pituitary in these thyroid dysfunctions.     

Changes in the hypothalamic-hypophyseal axis of mares associated with seasonal reproductive recrudescence

Four groups of mares, representing anestrus (AN; n = 8), early transition (ET; n = 7), late transition (LT; n = 8) and estrus (EST; n = 12) were used to examine changes in the hypothalamus and anterior pituitary during the period of transition from winter anestrus into the breeding season. Mares were of mixed breeding, between the ages of 3 and 20 years, and had shown normal patterns of estrous behavior and ovulation during the breeding season previous to this experiment. Hypothalamic content of gonadotropin-releasing hormone (GnRH) and anterior pituitary content of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. The number of receptors for GnRH in anterior pituitary tissue was also determined. There was no effect of stage of transition into the breeding season on receptors for GnRH or content of FSH (p greater than 0.05). Likewise, content of GnRH in the hypothalamus did not differ between the four groups (p greater than 0.05). However, pituitary content of LH increased progressively from anestrus to the breeding season (p less than 0.05). Means for the AN, ET, LT and EST groups were 1.1 +/- 0.2, 2.2 +/- 0.3, 6.3 +/- 1.4 and 15.2 +/- 1.8 micrograms LH/mg pituitary, respectively. In addition, serum concentrations of LH associated with the first ovulation of the year for 5 of the EST mares were significantly lower (p less than 0.01) than those associated with the second ovulation of the year.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats

The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3-5 months-old), and old acyclic (23-25 month-old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 micrograms melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11 +/- 1275.08 pg ml(-1); P < 0.05) and FSH concentrations (5879.28 +/- 1631.68 pg ml(-1); P < 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11 +/- 89.71 pg ml(-1)) and FSH concentrations (2070 +/- 301.62 pg ml(-1)) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo-pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats.     

The effect of intraventricular 6-hydroxydopamine on the content of oxytocin and vasopressin in the hypothalamus and pituitary gland of water-deprived rats

The effect of intraventricular 6-hydroxydopamine on the content of oxytocin and vasopressin in the hypothalamus and pituitary gland of water deprived rats. Acta Physiol. Pol., 1977, 28 (6): 497-504. Rats received one infusion of 200 microgram 6-hydroxydopamine with 25 microgram of ascorbic acid into the lateral cerebral ventricle. After 57 days some rats were deprived of water for 4, 8 or 12 days. Then, the animals were sacrificed by decapitation. Oxytocin was determined in extracts from the posterior pituitary lobe and hypothalamus by the method of Van Dongen and Hays, while the vasopressin content was determined by the method of Dekanski. It was found that 6-hydroxydopamine injection into the cerebral ventricles causes a rise in oxytocin content in the hypothalamus and prevents its fall during--4--12 days of dehydration.     

EGF binding site number of rat anterior pituitary is increased by chronic administration with dopaminergic agonist, CV 205-502]

In order to assess whether a chronic treatment with a dopamine agonist, CV205-502, could modulate anterior pituitary epidermal growth factor (EGF) binding sites, female Wistar rats were treated or not (controls) with CV205-502 0.25 mg/kg/day sc for 8 days. This treatment significantly reduced rats' pituitary weight and plasma prolactin levels when compared to controls (weight: 10.4 +/- 0.1 vs 11.1 +/- 0.1 mg, p less than 0.01; prolactin: 1.2 +/- 0.2 vs 4.9 +/- 0.5 ng/ml, p less than 0.01). These decreases were associated with a significant stimulation of the number of pituitary EGF binding sites Bmax: 16.7 +/- 2.3 vs 11.3 +/- 1.9 fmoles/mg proteins, p less than 0.01) with no significant effect on their affinity (Kd: 0.94 +/- 0.17 vs 0.95 +/- 0.14 nM). Therefore, the modulation of pituitary EGF binding sites might be one of the mechanisms by which the dopamine agonist, CV205-502, exerts its pharmacological effects on hormonal secretions and/or cell multiplication in the pituitary.     

Neurokinin A in the anterior pituitary of female rats: effects of ovariectomy and estradiol.

The effect of acute and chronic ovariectomy and the substitutive treatment with 17-beta estradiol and/or progesterone on anterior pituitary levels of neurokinin A (NKA) was studied in female rats. Acute ovariectomy did not result in significant changes of NKA in the anterior pituitary gland as compared with the levels in diestrous intact rats, but a single injection of 5 micrograms of estradiol in ovariectomized rats significantly decreased NKA levels in the anterior pituitary gland. Progesterone was without effect and did not modify the decrease of NKA in the anterior pituitary gland induced by estradiol. In rats examined 11 to 17 days after ovariectomy, NKA in the anterior pituitary gland was significantly higher than in diestrous intact rats. In the hypothalamus, ovariectomy resulted in decreased levels of NKA in the median eminence-arcuate nucleus. Estradiol significantly reduced NKA stores in the anterior pituitary gland but increased them in the whole hypothalamus and in the median eminence-arcuate nucleus. Thus, estradiol seems to be a powerful regulator of NKA stores in the adenohypophysis and also in the hypothalamus.     

Intrahypothalamic pituitary grafts elevate prolactin in the cerebrospinal fluid and attenuate prolactin release following ether stress

Anterior pituitary (AP) tissue grafted into the hypothalamus of female rats inhibits the luteotrophic prolactin (PRL) secretion which normally follows mating. Dopamine blockade has been shown to overcome this inhibition, suggesting that the grafts suppress PRL release from the in situ pituitary by the action of graft PRL increasing dopamine activity in the hypothalamus. To examine whether PRL levels in the cerebrospinal fluid (CSF) were elevated by the AP grafts, CSF samples were taken from 5 control rats and 10 rats bearing intrahypothalamic AP grafts. Mean PRL concentrations in the CSF of the control rats were 3.0 +/- 0.8 ng/ml. The grafted rats had significantly higher concentrations of PRL in their CSF, averaging 23.2 +/- 4.2 ng/ml (P less than 0.005). Plasma PRL concentrations were similar in the control and grafted rats. PRL release in response to 5 min of ether stress was examined in 8 control and 11 grafted rats. In control animals, PRL rose from 4.2 +/- 1.5 to 44.7 +/- 9.0 ng/ml following exposure to ether, but the response was significantly attenuated in the grafted rats, peaking at 9.3 +/- 1.4 ng/ml (P less than 0.001). This inhibition of response due to the grafts was evident within 1 week of graft placement. The results confirm that the presence of intrahypothalamic AP grafts led to the accumulation of supranormal PRL concentrations in the CSF. This elevated PRL suppressed pituitary PRL release in response to ether stress, probably by an autoregulatory feedback activation of the inhibitory tuberoinfundibular dopaminergic neurons in the hypothalamus.     

Alteration of somatostatin but not growth hormone-releasing factor pituitary binding sites in obese Zucker rats.

The present study was designed to determine whether the diminution of growth hormone (GH) secretion that occurs in obese Zucker rats is related to alterations of GH-releasing factor (GRF) or somatostatin (SRIF) pituitary binding sites. Cold saturation studies were performed in pituitary homogenates of 4-month-old lean and obese rats, using [125I-Tyr10]hGRF(1-44)NH2 as radioligand and [127I-Tyr10]hGRF-(1-44)NH2 as competitor, and in pituitary membrane preparations, using [125I-Tyr0, D-Trp8]SRIF14 as radioligand and [127I-Tyr0, D-Trp8]SRIF14 as competitor. In lean rats, analysis of the curves by the Ligand program revealed the presence of two distinct classes of GRF binding sites, the first being of high affinity (0.74 +/- 0.11 nM) and low capacity (118 +/- 31 fmol/mg protein), the second being of lower affinity (880 +/- 240 nM) and higher capacity (140 +/- 35 pmol/mg protein), and of a single class of SRIF binding sites (affinity: 0.40 +/- 0.12 nM; capacity: 24 +/- 6 fmol/mg protein). In obese rats, no difference was observed in GRF binding parameters for both classes of sites, but the concentration of somatostatin binding sites was reduced by 67% when compared to their lean littermates. These findings suggest that the SRIF pituitary receptors are down-regulated in obese Zucker rats and indicate that no alteration of GRF pituitary binding sites contribute to the blunted GH secretion observed in this model of obesity.     

The effects of neonatal androgenization of male rats on testosterone metabolism by the hypothalamus-pituitary-gonadal axis

Male rats were androgenized on the third postnatal day by a single injection of 1 mg testosterone propionate. The in vitro metabolism of [4-14C]testosterone by pituitary and hypothalamus homogenates was investigated at the age of 90 days. The pituitary and hypothalamus homogenates from control and neonatally androgenized animals converted [4-14C]testosterone to the same metabolites, mainly 5 alpha-reduced derivatives; the quantitative yield of 5 alpha-reduced metabolites was much higher in the pituitary homogenates of androgenized rats. The hypothalamic homogenates showed no differences. In the androgenized rats a very significant increase of the plasma FSH levels was measured while the LH levels were also augmented. The plasma levels of testosterone were not different from the values in control rats, notwithstanding a 25% reduction in testes weight. The present experiments appear to indicate that the neonatal androgenization results in an accentuation of the sexual dimorphism which normally exists in the pituitary of adult rats for the 5 alpha-reductase activity.     

Effect of Aging on 24-Hour Changes in Serotonin and Dopamine Turnover, and Somatostatin and Amino Acid Content, of the Rat Hypothalamus and Pituitary Gland

The effect of aging on neurotransmitter and peptide content in the hypothalamichypophysial unit has commonly been analyzed at single time points in the 24-h cycle. Since significant changes in circadian rhythmicity occur during aging, this study aimed to examine 24-h rhythmicity in hypothalamic and pituitary serotonin (5HT) and dopamine (DA) turnover and content, and somatostatin and amino acid content in 2 months-old and 18-20 months-old rats, killed at 6 different time intervals throughout the light-dark cycle. Aged rats showed suppressed or disrupted 24-h rhythms of 5HT and DA turnover and of somatostatin, glutamate, aspartate and taurine content (anterior hypothalamus), of 5HT and DA turnover and of somatostatin, glutamate, taurine and glycine content (medial hypothalamus) and of DA turnover and amino acid content (posterior hypothalamus). Twenty-four h variations in DA, somatostatin, aspartate, GABA and glycine content of the anterior hypophysis and in all parameters tested in the neurointermediate lobe became suppressed or disrupted in aged rats. Mean values generally decreased with age, except for DA content in the anterior pituitary lobe and aspartate content in the neurointermediate lobe. Conclusions: Examination of neurotransmitter and neuropeptide content at different times of the day is needed to analyze the effects of aging in the hypothalamic-hypophysial unit.     

The antihypertensive effect of ethylcholine aziridinium (AF64A), a cholinergic neurotoxin, in spontaneously hypertensive rats, following administration into the posterior hypothalamus

The aim of this study was to ascertain whether drug-induced cholinergic hypofunction in the posterior hypothalamus would affect the development and the maintenance of hypertension in hypertensive rats. Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were treated with AF64A, a neurotoxin which can irreversibly inhibit cholinergic transmission in vivo. AF64A or saline was injected bilaterally into the posterior hypothalamus of rats of two age groups: normotensive one month-old rats whose blood pressure was subsequently measured at the age of three months and hypertensive three month-old rats, whose blood pressure was measured four weeks later. In both age groups there was a significant fall in mean arterial blood pressure in SHR but not WKY rats. In SHR injected at the age of one month, there was a fall of at least 15.9 mm Hg, while in the rats injected at the age of three months there was a fall of 14.3 mm Hg. Heart rate in either strain was not affected. When AF64A was injected into the anterior hypothalamus of one month-old SHR, no antihypertensive effect was observed in these rats at the age of three months. These results show that cholinergic stimulation in the posterior hypothalamus may play a role in both the development and maintenance of hypertension in SHR.     

Cyclic AMP Generation in Medulla Oblongata and Hypothalamus of Hypertension-Prone and -Resistant Rats

Abstract: Accumulation of cAMP induced by noradrenaline (NA) was higher in the medulla oblongata (MO) of hypertension-prone (H) than in resistant (N) rats, 113 ± 3 vs. 72 ± 4 ( p < 0.01). In the hypothalamus (HYP) it was higher in N than in H rats, 148 ± 8 vs. 92 ± 6 ( p < 0.01). In both anterior and posterior HYP, the accumulation of cAMP was significantly higher in N than in H rats. cAMP accumulation, in the presence of increasing concentrations of phosphodiesterase inhibitor, showed significant strain differences in both MO and HYP. The observed strain differences in cAMP may be pertinent to the disparate susceptibility to hypertension of H and N rats.