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Biomedical subjects

J Culman

Publications and source records attributed to J Culman.

At least 55 records · Page 3Linked to original sources
PubMed1992

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia.

Animals↗
PubMed1992

Involvement of adrenergic and angiotensinergic receptors in the paraventricular nucleus in the angiotensin II-induced vasopressin release.

The role of hypothalamic paraventricular adrenoceptors and angiotensin II (ANG II)-AT 1 receptors in mediating the vasopressin (AVP) release into the plasma in response to i.c.v. and local paraventricular ANG II injections was investigated in conscious chronically instrumented rats. Noradrenaline (NA) administered bilaterally into the paraventricular nucleus (PVN) dose-dependently stimulated AVP release. Bilateral PVN microinjections of the alpha 1 adrenoceptor agonists methoxamine and phenylephrine, or of the alpha2 adrenoceptor agonist clonidine, did not affect plasma AVP when given alone, but increased plasma AVP when methoxamine and clonidine were given in combination. In contrast, PVN microinjections of both the beta 1 adrenoceptor agonist dobutamine and the beta 2 adrenoceptor agonist salbutamol significantly reduced basal plasma AVP. Bilateral PVN pretreatment with the alpha 1 and alpha 2 adrenergic antagonists prazosin, idazoxan and rauwolscine, but not of the beta 1 and beta 2 adrenoceptor antagonists atenolol and ICI 118 551, significantly attenuated the i.c.v. ANG II-induced AVP release. ANG II injected bilaterally into the PVN dose-dependently increased plasma AVP. Bilateral PVN pretreatment with the specific ANG II-AT 1 receptor antagonist losartan partially inhibited the i.c.v. ANG II-induced AVP release. We conclude: 1) Beta 1 and beta 2 adrenoceptors in the PVN exert an inhibitory action on basal AVP secretion. 2) ANG II can release AVP by directly stimulating its ANG II-AT 1 receptors in the PVN. 3) PVN mediated AVP release in response to periventricular ANG II-AT 1 receptor stimulation is at least partially effected through ANG II-AT 1 receptors in the PVN impinging on alpha adrenergic terminals.

Angiotensin II↗
PubMed1991

Distribution of angiotensin II receptor subtypes in rat brain nuclei.

Angiotensin II (ANG II) receptor subtypes in rat brain were characterized and quantified by competitive radioligand binding using [125I]Sar1 Ile8 angiotensin II ([125I]sarilesin) as a tracer and ANG II, sarilesin and the subtype selective ligands DuP 753 (AT1) and CGP 42112A (AT2) as competitors. The distribution of AT1 and AT2 receptors was determined in midbrain, brainstem, hypothalamus as well as in individual hypothalamic and periventricular nuclei. Whereas in midbrain and brainstem the AT1: AT2 ratio was 40%: 60% and 70%: 30% respectively, the AT1 receptors were by far predominant in hypothalamus and in the nuclei investigated. Interestingly, we found that approximately 25% of the ANG II receptors in hypothalamus did not bind DuP 753 even at 0.1 mM. These sites which bind CGP 42112A, ANG II and sarilesin may represent a third ANG II receptor subtype.

Angiotensin II↗
PubMed1991

Localization of the substance P-induced cardiovascular responses in the rat hypothalamus.

Intracerebroventricular injection of substance P (SP) has been reported to induce a typical cardiovascular defense response characterized by an increase in blood pressure, heart rate, sympathetic efferent activity, hindlimb vasodilatation and mesenteric vasoconstriction. In this study we employed microinjections of SP to localize the hypothalamic areas in which SP elicits the activation of the cardiovascular system. SP (550 pmol) injected into the anterior hypothalamus (AH) produced, after a short latency, a marked increase in mean arterial pressure and heart rate. In the ventromedial hypothalamus, the magnitude of the cardiovascular response to SP was identical to that in the AH, but the response was delayed. SP injected into the posterior hypothalamus failed to induce any cardiovascular response. These results suggest that the anterior and ventromedial parts of the hypothalamus are responsible for eliciting the central cardiovascular effects of SP in conscious rats.

Animals↗
PubMed1991

Regulation of corticotropin-releasing hormone and pituitary-adrenocortical response during acute and repeated stress in the rat.

The hormonal response of the pituitary-adrenocortical system to acute or repeated immobilization (IMO) stress was studied in rats. Plasma ACTH response was markedly reduced in repeatedly stressed rats compared to acutely stressed ones, but no differences in plasma corticosterone responses were seen. Acute but not repeated IMO caused a marked reduction of the ACTH content in the anterior pituitary, but no changes of the ACTH content were found in the intermediate-posterior pituitary or in the median eminence (ME) in animals exposed to either acute or repeated stress. Acute IMO elicited a marked reduction of the content of corticotropin releasing hormone (CRF) in the ME. The basal concentration of CRF in the ME of repeatedly stressed rats did not differ from that in intact controls; subsequent exposure of repeatedly stressed rats to IMO caused an insignificant reduction of the CRF content in the ME. In response to peripheral injections of CRF (50 and 500 ng per rat) a dose dependent increase of plasma ACTH was observed in both control and repeatedly stressed rats, however, no differences in ACTH responses to CRF were seen between these two groups. Plasma corticosterone response to the high dose of peripherally administered CRF did not differ between control and repeatedly stressed rats, while plasma corticosterone response to the low dose of CRF was greater in repeatedly stressed rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1988

Effect of corticosterone treatment and adrenalectomy on phenylethanolamine N-methyltransferase and catecholamines in brain stem and hypothalamic nuclei and superior cervical ganglion of rats.

The effects of corticosterone treatment and adrenalectomy with or without corticosterone replacement on the activity of phenylethanolamine N-methyltransferase (PNMT) and catecholamine content has been studied in isolated brain stem nuclei containing adrenergic and noradrenergic nerve cell bodies, hypothalamic nuclei and in the superior cervical ganglion (SCG) of adult rats. Changes of PNMT activity were found only in a few brain stem areas. In adrenalectomized rats, PNMT activity was decreased in Cl area and in the locus coeruleus, but after corticosterone replacement it returned to the control values. The treatment of rats with corticosterone resulted in a rise of PNMT activity only in C2 area. No significant changes in PNMT activity were seen in the hypothalamic areas in any experimental group of rats. The observed changes of PNMT activity occurred without any measurable changes of noradrenaline (substrate) or adrenaline (product of the reaction catalysed by PNMT). Our results may suggest the involvement of brain stem adrenaline and noradrenaline producing neurons in the central modulation of the pituitary-adrenal function. The basal PNMT activity in SCG of adult rats was very low, but the treatment of rats with high dose of corticosterone or corticosterone replacement to adrenalectomized rats increased PNMT activity in the SCG to the same extent.

Adrenal Glands↗
PubMed1988

3-H-ketanserin (serotonin type 2) binding in the rat frontal cortex: effect of immobilization stress.

The number of 3H-ketanserin (5-HT2) binding sites in rat frontal cortex was estimated in groups of male rats subjected to a single or repeated immobilization stress (IMO). After an acute IMO for 30 or 120 min the number of 5-HT2 binding sites was significantly increased. Similar increase was found even in a group subjected for 120 min IMO for 6 consecutive days and then allowed 24 h rest (i.e. repeatedly stressed controls). If similarly treated animals were subjected to 30 min IMO after 24 h rest, the number of binding sites was increased compared to repeatedly stressed controls, but this was not the case after 120 min IMO. No significant changes of 5-HT2 receptor affinity to 3H-ketanserin were found. The changes of the ratio of 5-hydroxyindolacetic acid/5-hydroxytryptamine were similar to those of binding sites. It was concluded that the enhanced number of cortical 5-HT2 receptor binding sites may result from accelerated serotonin turnover induced by stress, but the results did not indicate any direct association between the serotonin turnover and 5-HT receptor function in the rat frontal cortex.

Animals↗
PubMed1987

Distribution of phenylethanolamine-N-methyltransferase in the rat heart: effect of 6-hydroxydopamine.

The distribution of phenylethanolamine-N-methyltransferase (PNMT), the epinephrine-forming enzyme in the adult rat heart atria and ventricles was studied. The activity of the enzyme in the hearts of adult rats is very low; a significantly higher activity was found in the atria than in the ventricles. A significant increase in PNMT activity was found in all heart areas examined in 6-hydroxydopamine-treated rats compared to vehicle-treated rats. The increased PNMT activity might reflect compensatory or adaptation processes secondary to the destruction of the peripheral sympathetic nerve terminals.

Animals↗
PubMed1987

A radiometric assay for phenylethanolamine N-methyltransferase and catechol O-methyltransferase in a single tissue sample: application to rat hypothalamic nuclei, pineal gland, and heart.

A simple and highly sensitive method for simultaneous assay of phenylethanolamine N-methyltransferase (PNMT) and catechol O-methyltransferase (COMT) is described. These enzymes are determined in a single tissue homogenate using S-[methyl-3H] adenosyl-L-methionine as methyl donor and sequentially incubating with the substrates phenylethanolamine and epinephrine. The radioactive products of the enzymatic reactions, N-methylphenylethanolamine and metanephrine, are extracted and then separated by thin-layer chromatography. The identity of the reaction products has been established chromatographically and the conditions for both enzymatic reactions in the assay procedure have been defined. Measurement of PNMT activity in the rat pineal gland or in minute fragments of other tissues (e.g., brain nuclei) has not been possible using previously described methods. Activities of PNMT and COMT in the rat pineal gland, various hypothalamic nuclei, and the auricular and ventricular myocardia are herein reported.

Animals↗
PubMed1987

Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure.

Plasma epinephrine (EPI), norepinephrine (NE), beta-endorphin, and corticotropin (ACTH) responses were measured during insulin-induced hypoglycemia in normal subjects and in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). In normal subjects, there was a striking rise in EPI, NE, beta-endorphin, and ACTH following the nadir of hypoglycemia. Both beta-endorphin and ACTH responses were significantly lower than normal in patients with MSA, in contrast to normal levels in IOH patients. No correlation was observed between the degree of adrenergic insufficiency and the beta-endorphin and ACTH responses. The normal peptide responses in IOH are consistent with involvement limited to the peripheral sympathetic nervous system, whereas lesions in the central nervous system in MSA interfere with release of beta-endorphin and ACTH in response to hypoglycemia. The strong correlation between beta-endorphin and ACTH levels is consistent with their common origin. Peripheral adrenergic activity is not essential for beta-endorphin and ACTH release in humans.

Adrenal Glands↗
PubMed1987

Sympathoadrenal activity facilitates beta-endorphin and alpha-MSH secretion but does not potentiate ACTH secretion during immobilization stress.

The potential involvement of the sympathoadrenal system in stress-induced secretion of peptides from the intermediate lobe of the pituitary gland and the activation of the pituitary-adrenal axis was studied. Male Wistar rats were subjected to control procedures, to sympathectomy by chronic administration (8 weeks) of guanethidine and/or to medullectomy by adrenal enucleation 9 weeks prior to exposure to forced immobilization stress for various periods of time. In intact or sham-operated rats, immobilization caused a prompt increase of circulating norepinephrine, epinephrine (EPI), corticosterone and of immunoreactive adrenocorticotropic hormone (ACTHi), alpha-melanocyte-stimulating hormone (alpha-MSHi) and beta-endorphin (beta-ENDi). Peak levels of pituitary hormones were found after 10 min of stress exposure, but fell to less than 30% of these levels after 2.5 h of immobilization. Adrenal medullectomy, which abolished the stress-induced release of EPI, reduced the acute increase of plasma alpha-MSHi and beta-ENDi, but did not influence the acute increase of plasma ACTHi during immobilization stress. Also in medullectomized plus sympathectomized rats, the initial stress response of circulating ACTHi was not different from that of controls. Adrenal medullectomy with or without additional sympathectomy caused a marked increase in plasma ACTHi concentrations after prolonged stress exposure. We conclude that: catecholamines originating from the adrenalmedulla facilitate the stress-induced secretion of intermediate lobe peptides (alpha-MSHi, beta-ENDi); catecholamines from the sympathoadrenomedullary system do not contribute to the acute release of ACTH during immobilization stress; the sympathoadrenomedullary system is involved in the secondary reduction of circulating ACTHi levels seen during prolonged stress.

Adrenal Medulla↗
PubMed1986

Neurotransmitter levels in the hypothalamus during postnatal development of rats.

The content of norepinephrine (NE), epinephrine (E), dopamine (DA) and serotonin (5-HT) in the rat hypothalamus was determined at four hours time interval during 24 hours period at the age of 12, 23, 27 and 75 days. It was found that the content of NE in the hypothalamus is low in 12 day-old rats, and during the postnatal period a gradual increase of NE was noted. The content of E in the hypothalamus is low in 12- to 27-day-old rats and an important increase was found in adult animals. The high values of DA and 5-HT concentration were found in the hypothalamus of 12-day-old rats and a transient decrease of 5-HT and DA at the age of 23 days was noted, further an important increase of the content of both neurotransmitters in the hypothalamus was demonstrated later in life. The presence of circadian rhythm of hypothalamic NE, E, DA and 5-HT content was found in 12-, 23-, 27-day-old and in adult rats overfed or underfed during the suckling period. However, no significant correlation was observed between the NE and E levels in the hypothalamus and the diurnal fluctuations of plasma corticosterone concentrations. In adult animals an inverse correlation between the plasma corticosterone level and hypothalamic 5-HT content was noted. In young 12- and 23-day-old rats the correlation between 5-HT in the hypothalamus and corticosterone in the plasma was positive. These results indicate that the shift of peak in plasma corticosterone levels during postnatal ontogenesis of rats observed in previous experiments is not dependent on the changes in diurnal fluctuation of hypothalamic neurotransmitter concentrations.

Age Factors↗
PubMed1985

Serotonin in individual hypothalamic nuclei of rats after space flight on biosatellite Cosmos 1129.

The experiment on Cosmos 1129 was based on our results obtained in rats exposed to single or repeated restrain stress in the laboratory. These results have convincingly demonstrated a significant increase of serotonin concentration (5-HT) in the hypothalamus in acutely stressed rats. This response, which was found also in the isolated hypothalamic nuclei, was diminished in repeatedly (40 times) immobilized rats. While the concentration of 5-HT was unchanged in the majority of the hypothalamic nuclei of animals subjected to cosmic flight, an increase was recorded only in the supraoptic nucleus (NSO) and a decrease in the periventricular nucleus. These findings demonstrate that only few areas of the hypothalamus respond to cosmic flight with changes of 5-HT concentration and suggest either that long-term cosmic flight cannot be an intensive stressor or that during the flight the rats became already adapted to its long-term effect. However, the exposure of flight rats to repeated immobilization stress resulted in a significant increase of 5-HT in the NSO, para-ventricular and dorsomedial (NDM) nuclei. It should be noted that we have never seen any changes of 5-HT concentration, tryptophan hydroxylase and monoamineoxidase activities in repeatedly (40 times) immobilized rats. On the other hand, the increase of 5-HT concentration in the NDM is a typical finding after seven exposures of rats to immobilization on Earth, daily for 150 min. In the experiment COSMOS 1129 such an increase of 5-HT concentration in the NDM was found not only in the flight group but also in the control group of rats subjected to five daily exposures of immobilization stress. With respect to these findings, the increased 5-HT concentrations observed in some isolated hypothalamic nuclei in the flight group of rats exposed after landing to repeated immobilization stress suggest that long-term space flight and the state of weightlessness do not represent a stressogenic factor with respect to the serotoninergic system in the hypothalamus.

Animals↗
PubMed1984

Serotonin and tryptophan hydroxylase in isolated hypothalamic and brain stem nuclei of rats exposed to acute and repeated immobilization stress.

The effect of acute and repeated immobilization stress on serotonin concentration and tryptophan hydroxylase activity in some isolated hypothalamic and brain stem nuclei was measured using a special microdissection technique and sensitive isotopic-enzymatic microassays. In acutely immobilized rats serotonin concentration was increased in the median eminence, ventromedial and dorsomedial nuclei. In repeatedly immobilized rats increased serotonin concentration was recorded in the dorsomedial nucleus immediately after seven, and in the median eminence after forty consecutive daily exposures to immobilization. Decreased tryptophan hydroxylase activity was found in the suprachiasmatic nucleus after seven exposures to immobilization stress. Acute and repeated immobilization stress failed to produce any changes of serotonin concentration in the isolated brain stem nuclei studied, and of tryptophan hydroxylase activity in the dorsal raphe nucleus and n. centralis superior. The increased tryptophan hydroxylase activity observed without any changes in serotonin concentration in the locus coeruleus after the 7th immobilization may suggest an increased synthesis and release rate of serotonin in serotonergic nerve terminals in this area. The changes of serotonin concentration in some hypothalamic nuclei under the first exposure of rats to stress indicate the involvement of serotonin in the activation of the pituitary-adrenocortical system as well as in other neuroendocrine reactions initiated in the hypothalamus during acute stress. On the basis of the results presented, the presumed role of the serotonergic system in the regulation of pituitary-adrenocortical stress response in repeatedly stressed rats has not been established. The reported response of brain tryptophan hydroxylase to the release of endogenous corticosterone could not be confirmed in our experiments.

Animals↗
PubMed1984

Decreased corticotropin-releasing factor-like immunoreactivity in rat intermediate and posterior pituitary after stalk section.

We determined the corticotropin-releasing factor(CRF)-like immunoreactivity by radioimmunoassay in intermediate and posterior pituitary lobes of stalk-sectioned and sham-operated control rats. The antigenic determinant read by the CRF antibody used was contained within the region of amino acids 26 (Gln) to 37 (Leu) of the molecule. Intermediate and posterior lobes of control rats contained similar amounts of CRF (591 +/- 78 and 487 +/- 34 pg/mg protein, respectively). The section of the pituitary stalk produced a marked decrease in CRF-like immunoreactivity in both structures. The CRF content on the intermediate lobe after stalk section was 62 +/- 17 pg/mg protein, a decrease of 90%, and that of the posterior lobe was 90 +/- 13 pg/mg protein, an 83% decrease. Our results suggest that most of the CRF-like immunoreactivity in the rat intermediate and posterior pituitary lobes is contained in nerve fibers of brain origin and support the hypothesis of a role of CRF in the release of intermediate and posterior lobe peptides.

Animals↗
PubMed1983

Pituitary-thyroid function during acute immobilization stress in rats.

In nine experiments a total of 394 male Wistar rats weighing about 300 g was used. In each experiment, one intact control group was used and several other groups were subjected to immobilization (IMO) for 2 to 240 min in a prone position by inserting their heads through steel wire loops fixed on a board and by fasting their limbs to four metal strips by adhesive tape. All animals were killed by decapitation and the levels of thyrotropin (TSH), thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) in plasma were estimated by radioimmunoassay. In one experiment, significant changes in the level of all hormones measured were found within 2 to 15 min of IMO, e.g. an increase of TSH, T4 and rT3 and a decrease of T3. Later (i.e. between 30 and 240 min) the level of TSH, T4 and T3 was repeatedly found to be significantly decreased almost in all experiments as compared to controls. In contrast, a significant increase of rT3 was found only in one out of 7 experiments, the values in other ones being unchanged. Corresponding changes of hormone levels were observed when IMO for 150 min was repeated daily for 7 or 40 days and the animals were sacrificed immediately after the last stress, while one day of rest after such procedures as well as after a single IMO for 150 min appeared to be sufficient for the levels to return to control values.

Animals↗
PubMed1983

Immediate increase of thyroid hormone release during acute stress in rats: effect of biogenic amines rather than that of TSH?

An increase of thyroxine (T4; 36% in average) and 3,5,3'-triiodothyronine (T3; 9% in average) levels in plasma was found in rats after 2 min of immobilization stress (IMO), while later (from 5 to 240 min of IMO) the level of both hormones decreased sharply. This increase was prevented by ip injection of phenoxybenzamine (4 or 16 mg kg-1), prazosin (2.5 mg kg-1), yohimbin (4 or 16 mg kg-1) and fluoxetine (10 mg kg-1) at 60 min before IMO, but similar injections of phentolamine (4 or 16 mg kg-1), tolazoline (4 or 16 mg kg-1), methysergide (10 mg kg-1), cyproheptadine (10 mg kg-1) as well as of lower doses of prazosin (0.6 or 1.2 mg kg-1) did not show such an effect. The level of TSH was increased after 2 min IMO too, but this was considered to be a separate phenomenon from the increase of T4 and T3, since in several groups injected with some of the above drugs the level of TSH was decreased together with increased levels of T4 and T3. It is suggested that the acute release of thyroid hormone might be due to the effect of biogenic amines which may be blocked by some alpha-adrenergic blocking agents. Since neither adrenalectomy nor adrenal-medullectomy prevented such a release, it may be concluded that circulating catecholamines of adrenal origin did not play any role in this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗