Search PubMed⌕ Search

Biomedical subjects

M Palkovits

Publications and source records attributed to M Palkovits.

At least 109 records · Page 6Linked to original sources
PubMed1996

Immunohistochemical localization of calcitonin gene-related peptide in the terete nucleus of the rat hypothalamus.

The topographical distribution of calcitonin gene-related peptide (CGRP) containing neuronal elements in the posterior hypothalamus has been re-examined by means of indirect labeled immunohistochemistry in the rat. In contrast to previous findings, no CGRP-like immunoreactive neuronal perikarya were present in the premamillary nuclei, but they form a small group of cells, which is identical to the recently described terete nucleus. In coronal sections, this small and rounded cluster of intermingled CGRP-immunopositive perikarya and fibers is situated in the lateral hypothalamus at the premamillary level, ventrolateral to the fornix. Perikarya, dendrites, presynaptic terminals, as well as nonmyelinated and some myelinated axons were labeled by CGRP-like immunoreactive material within and in the immediate vicinity of the terete nucleus. On some of the CGRP-positive neurons, neuropeptide Y-immunoreactive axon terminals establish synaptic contacts.

Animals↗
PubMed1996

Amino acid distribution in immature rat brain.

We compared the levels of amino acids in the free pool in 6 regions (cerebral cortex, olfactory bulb, substantia nigra, globus pallidus, caudate nucleus, and spinal cord) in the newborn rat brain. The amino acid distribution was heterogeneous, with the area of highest concentration containing 2-3 fold as much as the lowest area. These differences were considerably less than those previously found for adult brain. Although some areas often contained high levels of amino acids, and others mostly low levels, the distribution of the various amino acids was highly variable. This heterogeneity of distribution in the newborn brain was different from that in the adult brain. We conclude that there is significant heterogeneity of amino acid distribution, that it is different for each amino acid, and that it undergoes major changes during development.

Aging↗
PubMed1995

Effects of various stressors on in vivo norepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis.

The hypothalamic-pituitary adrenocortical (HPA) system and sympathoneural and adrenomedullary systems are major effector systems that serve to maintain homeostasis during stress. Corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus, a determinant of both HPA and autonomic responses to stress, is under the control of many neurotransmitters and neuropeptides. Norepinephrine (NE) potently stimulates CRH neurons in the PVN; however, the physiologic role of NE in stress-induced activation of the HPA is unknown. In the present study we exposed animals to various stressors (immobilization (IMMO), cold (COLD), hemorrhage (HEM), hypoglycemia elicited by insulin administration (INS), pain and tissue damage caused by formalin injection (FORM) and sc injection of physiological saline (SAL), all of which are known to activate the HPA axis. Injection of physiological saline iv was used as a control. In vivo microdialysis was used to assess stressor- and intensity-specific activation of the PVN noradrenergic system, based on measurements of NE, its intraneuronal metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Simultaneously with microdialysate collections, blood samples were obtained via catheters in the femoral artery to measure plasma ACTH and corticosterone (CORT) levels as dependent measures, to assess stress-induced activation of the HPA axis. At their highest intensities, all the stressors significantly increased levels of PVN microdialysate NE, DHPG, and DOPAC, and plasma ACTH and CORT. PVN NE levels varied across stressors, with IMMO and FORM more potent than INS, COLD, or HEM. INS and HEM evoked proportionately larger plasma ACTH responses than did IMMO, FORM, and COLD. Plasma CORT responses were largest during IMMO, FORM, and HEM. Except for COLD and HEM, there was a strong correlation of plasma ACTH levels with levels of NE, DHPG, and DOPAC in PVN microdialysate. The data suggest that, except for COLD or HEM, there is a strong positive correlation of PVN noradrenergic activation and activity of the HPA axis. With stressors such as IMMO and FORM, NE synthesis, reflected by DOPAC changes, is strongly positively correlated with activity of the HPA axis. Furthermore, the results indicate substantial stressor specificity of PVN catecholaminergic and of HPA responses to different stressors and are inconsistent with a founding tenet of Selye's stress theory, the doctrine of nonspecificity, which defines stress as the nonspecific response of the body to any demand.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Neurotensin and neuromedin N brain levels after fornix transection: evidence for an efficient neurotensin precursor processing in subicular neurons.

High levels of neurotensin/neuromedin N precursor mRNA, but few if any NT-positive perikarya have been detected in the dorsal subiculum of the adult rat or human hippocampus. This apparent discrepancy was tentatively ascribed to a lack of precursor mRNA translation or to a poor precursor posttranslational processing in neurons of the hippocampus. Another hypothesis is that in long neuronal pathways, maturation of neuropeptide precursors and derived peptides occurs during axonal transport to terminals, a process which accounts for the lack of peptide detection in cell bodies. In order to test this hypothesis, we performed surgical transection of the fornix to interrupt axonal transport of putative NT/NN products arising from the dorsal hippocampus and measured NT and NN levels in different brain regions. In the mamillary bodies, the main projection area of the dorsal subiculum, NN and NT levels were highly reduced 4 or 14 days after the septo-hippocampal transection which was correlated with a slight increase in NN and NT levels in the dorsal hippocampus and the retrosplenial cortex of 4 days lesioned animals. An increase in hypothalamic NN levels was also detected 14 days after the lesion. These data suggest that the peptide precursor processing can take place during the axonal transport, as shown here for neurotensin and neuromedin N from subicular neurons to their efferent brain areas such as the mamillary bodies.

Animals↗
PubMed1995

Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in human brain nuclei.

Concentrations of pituitary adenylate cyclase activating polypeptide (PACAP) in 79 microdissected human brain regions from adult 40- to 80-year-old adult males were measured by radioimmunoassay. Although PACAP was detectable in all of the brain nuclei investigated, the distribution of the peptide was regionally very heterogeneous. The ratio of the highest to the lowest concentrations measured in brain regions exceeded 160:1. The highest concentrations were found in the dorsal vagal complex, the bed nucleus of the stria terminalis, the median eminence-pituitary stalk, and in the periventricular and paraventricular hypothalamic nuclei. They were followed by some hypothalamic (supraoptic and ventromedial), preoptic and brainstem nuclei. High concentrations were also measured in the septum pellucidum, periaqueductal and spinal gray matters, the motor facial, and in the spinal nucleus of the trigeminal nerve. The distribution pattern of PACAP in the human brain was unique; it did not show any similarities to the distributions of other neuropeptides in the central nervous system.

Adult↗
PubMed1995

Calcitonin gene-related peptide innervation of A2-catecholamine cells in the nucleus of the solitary tract of the rat.

By using double immunolabeling light and electron microscopic techniques, dense neuronal network of calcitonin-related peptide (CGRP) has been visualized in the nucleus of the solitary tract with complete overlapping of the tyrosine hydroxylase (TH)-containing cells. TH-immunoreactive perikarya and dendrites were seen in synaptic contact with CGRP-immunopositive fibers, indicating that CGRP, by carrying sensory signals may influence autonomic regulatory mechanisms in the NTS through local catecholaminergic neurons.

Animals↗
PubMed1995

Effects of immobilization on in vivo release of norepinephrine in the bed nucleus of the stria terminalis in conscious rats.

Release of norepinepriine (NE) and its metabolites in the bed nucleus of the stria terminalis (BNST) was examined using in vivo microdialysis in conscious rats before, during and after 2 h of immobilization. Microdialysate levels of NE and of dihydroxyphenylglycol (DHPG) increased by 170-290% above basal levels during the 1st h of immobilization and decreased gradually thereafter. In contrast, levels of dihydroxyphenylacetic acid (DOPAC) increased gradually over the entire period of immobilization, peaking at 110% above baseline levels. These findings indicate that in rats a single immobilization is attended by increased synthesis, release and reuptake of NE within the BNST. The results are consistent with previous findings relating to stress-induced release of NE in the hypothalamic paraventricular nucleus, central nucleus of the amygdala and cerebral cortex and suggest concurrent noradrenergic activation in several brains centers during acute stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis studies.

The hypothalamic-pituitary-adrenocortical (HPA) axis and the autonomic nervous system are major effector systems that serve to maintain homeostasis during exposure to stressors. In the past decade, interest in neurochemical regulation and in pathways controlling activation of the HPA axis has focused on catecholamines, which are present in high concentrations in specific brain areas--especially in the hypothalamus. The work described in this review has concentrated on the application of in vivo microdialysis in rat brain regions such as the paraventricular nucleus (PVN) of the hypothalamus, the central nucleus of the amygdala (ACE), the bed nucleus of the stria terminalis (BNST), and the posterolateral hypothalamus in order to examine aspects of catecholaminergic function and relationships between altered catecholaminergic function and the HPA axis and sympathoadrenal system activation in stress. Exposure of animals to immobilization (IMMO) markedly and rapidly increases rates of synthesis, release, and metabolism of norepinephrine (NE) in all the brain areas mentioned above and supports previous suggestions that in the PVN NE stimulates release of corticotropin-releasing hormone (CRH). The role of NE in the ACE and the BNST and most other areas possessing noradrenergic innervation remains unclear. Studies involving lower brainstem hemisections show that noradrenergic terminals in the PVN are derived mainly from medullary catecholaminergic groups rather than from the locus ceruleus, which is the main source of NE in the brain. Moreover, the medullary catecholaminergic groups contribute substantially to IMMO-induced noradrenergic activation in the PVN. Data obtained from adrenalectomized rats, with or without glucocorticoid replacement, and from hypercortisolemic rats suggest that glucocorticoids feedback to inhibit CRH release in the PVN, via attenuation of noradrenergic activation. Results from rats exposed to different stressors have indicated substantial differences among stressors in eliciting PVN noradrenergic responses as well as of responses of the HPA, sympathoneural, and adrenomedullary systems. Finally, involvement of other areas that participate in the regulation of the HPA axis such as the ACE, the BNST, and the hippocampus and the importance of stress-induced changes in expression of immediate early genes such as c-fos are discussed.

Adrenal Cortex↗
PubMed1995

Molecular neurobiology and pharmacology of the vasopressin/oxytocin receptor family.

1. VP and OT mediate their wealth of effects via 4 receptor subtypes V1a, V1b, V2, and OT receptors. 2. We here review recent insights in the pharmacological properties, structure activity relationships, species differences in ligand specificity, expression patterns, and signal transduction of VP/OT receptor. 3. Furthermore, the existence of additional VP/OT receptor subtypes is discussed.

Amino Acid Sequence↗
PubMed1995

Immunohistochemical mapping of neuropeptides in the premamillary region of the hypothalamus in rats.

The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone-releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers.

Animals↗
PubMed1995

Decreased stress responsivity of central and peripheral catecholaminergic systems in aged 344/N Fischer rats.

We investigated the effects of stress on central and peripheral sympatho-adrenal and sympatho-neural functions in healthy, intact young (3-4 mo) and aged (24 mo) male Fischer 344/N rats. Extracellular fluid (ECF) levels of the catecholamines norepinephrine (NE), dihydroxyphenylglycol (DHPG), methoxyhydroxyphenylglycol (MHPG), and dihydroxyphenylacetic acid (DOPAC) were obtained by microdialysis in the paraventricular nucleus (PVN) of the hypothalamus at baseline and during immobilization (IMMO). The baseline levels of these substances were similar in both age groups, and their concentrations increased significantly in response to IMMO. The IMMO-induced increases of NE and MHPG, however, were significantly smaller in old than in young rats. Plasma levels of the catecholamines NE, DHPG, MHPG, DOPAC, dihydroxyphenylalanine (DOPA), epinephrine (EPI), dopamine (DA), and HVA were also determined in young and old rats during IMMO. Basal levels of these substances were significantly higher in old than in young rats. The magnitude of the IMMO-induced increases in the majority of these compounds however, was significantly smaller in old than in young rats. We conclude that, at the basal state, aging in the Fischer rat is associated with normal PVN ECF, but high plasma catecholamine levels; at stress state, however, old rats have substantially lesser activation of their central and peripheral catecholaminergic systems than young rats.

Adrenergic Fibers↗
PubMed1995

Decreased central and peripheral catecholaminergic activation in obese Zucker rats.

The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteronism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system.

Adrenocorticotropic Hormone↗
PubMed1995

Regulation of corticotropin-releasing hormone receptor messenger ribonucleic acid in the rat brain and pituitary by glucocorticoids and stress.

Glucocorticoids and stress are known to influence the synthesis of corticotropin-releasing hormone (CRH) at a variety of sites in brain, including the hypothalamus and amygdala. The recent cloning of the CRH receptor (CRH-R) enabled us to determine whether glucocorticoids or stress influenced CRH action via regulation of CRH-R. We, therefore, used in situ hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (AP), amygdala, and bed nucleus of the stria terminalis (BNST) under several conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat.day) up to 14 days and pellet implant (200 mg) for 14 days, decreased CRH-R mRNA in the PVN and lateral and basolateral nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat.day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also decreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA. In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX+CORT rats), acute (2-h) and repeated (2 h daily for 14 days) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX+CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected CRH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CRH synergistically decrease CRH-R mRNA levels in the AP, and that at least high CORT has an inhibitory effect on PVN CRH-R mRNA levels. However, stress input can override such inhibitory effects and thus up-regulate CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amygdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA.

Adrenocorticotropic Hormone↗
PubMed1995

Catecholaminergic inhibition by hypercortisolemia in the paraventricular nucleus of conscious rats.

Administration of glucocorticoids decreases the release of corticotropin-releasing hormone and in vitro turnover of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, and immobilization (IMMO) markedly increases NE release and stimulates corticotropin-releasing hormone neurons in the PVN. This study assessed whether hypercortisolemia affects in vivo indexes of catecholaminergic activation in the PVN. Microdialysis was used to simultaneously measure PVN microdialysate concentrations of NE, the neuronal NE metabolite dihydroxyphenylglycol, the extraneuronal NE metabolite methoxyhydroxyphenylglycol, and the dopamine metabolite dihydroxyphenylacetic acid before, during, and after 2 h of IMMO. Catecholamine synthesis was examined based on elevations of 3,4-dihydroxyphenylalanine levels after local perfusion with NSD-1015, an inhibitor of L-aromatic acid decarboxylase. Cortisol (CORT; 25 mg/kg.day) or vehicle (VEH; saline) was infused sc for 7 days via an osmotic minipump. CORT-treated rats had lower basal NE, dihydroxyphenylglycol, methoxyhydroxyphenylglycol, and dihydroxyphenylacetic acid levels and significantly smaller levels of all these compounds during IMMO than VEH-treated rats. CORT-treated rats also had less NSD-1015-induced accumulation of microdialysate 3,4-dihydroxyphenylalanine at baseline and during IMMO than VEH-treated rats. Basal and IMMO-induced plasma ACTH and corticosterone responses were reduced in CORT-treated rats. The results indicate that chronic hypercortisolemia decreases basal levels and stress-induced increments in indexes of release, metabolism, turnover, and synthesis of catecholamines in the PVN and suggest that glucocorticoids restrain the limit of hypothalamo-pituitary-adrenocortical axis activation during stress by attenuating catecholamine synthesis and release in the PVN.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Angiotensin II-induced hypertension: effects on central and peripheral atrial natriuretic peptide.

Angiotensin (Ang) II and atrial natriuretic peptide (ANP) have opposing effects on blood pressure, sympathetic activity, vasopressin and ACTH secretion, salt appetite, and drinking. We observed their interaction by infusing Ang II (7.2 nmol/h) into the peritoneum (i.p.) or into the lateral ventricle (i.c.v.) of rats with osmotic minipumps for seven days. At sacrifice, rats receiving Ang II-i.c.v. had a systolic blood pressure of 184 +/- 3 (SEM) mmHg, those receiving Ang II-i.p. had 159 +/- 5 mmHg (p < 0.05), while controls had 109 +/- 2 and 110 +/- 2 mmHg, respectively (p < 0.05). Drinking and urine volume increased similarly in rats receiving Ang II by either route, while Uosm decreased. Renin (PRA) values were lower (p < 0.05) in rats receiving Ang II-i.c.v. (0.7 +/- 0.2 ng Ang l/ml/h) or Ang II-i.p. (0.9 +/- 0.2) than in the respective controls (2.3 +/- 0.7 and 2.0 +/- 0.3). Plasma ANP values with Ang II-i.c.v. (18 +/- 1.6 pg/ml) or with Ang II-i.p. (49 +/- 6) were also lower (p < 0.05) than respective controls (89 +/- 12, 76 +/- 4). Vasopressin (AVP) concentrations in the plasma were not influenced by the regimens. In the brain, the ANP contents in areas of the so-called AV3V-region (organum vasculosum laminae terminalis, preoptic periventricular nucleus, medial preoptic nucleus) were similarly and significantly reduced by both Ang II-i.c.v. and Ang II-i.p.. ANP values were also reduced in the median eminence by both types of Ang II-treatment, while ANP concentrations in the supraoptic nucleus were increased. The data show that Ang II infusions producing a chronic rise in blood pressure exert similar effects on drinking behavior, PRA, and ANP concentrations in blood and brain. The AV3V area may be pivotal to both models.

Angiotensin II↗
PubMed1995

Trifluoperazine modulates [3H]resiniferatoxin binding by human and rat vanilloid (capsaicin) receptors and affects 45Ca uptake by adult rat dorsal root ganglion neurones.

Optimum treatment of neuropathic pain includes the use of adjuvant analgesics such as antipsychotic drugs and tricyclic antidepressants. Although the mechanism of their analgesic action is not known, it is possible that such agents act directly on pain pathways. The ability of capsaicin and its analogs to selectively deactivate primary afferent neurons provides a basis for their use in human therapy to relieve a number of chronic pain conditions. We examined whether the phenothiazine antipsychotic drug trifluoperazine (TFP) as well as other neuroleptics and tricyclic antidepressants have an effect on the agonist binding properties and the activation of the human and rat vanilloid receptors. Binding of [3H]resiniferatoxin (RTX) to membrane preparations of human dorsal horn and rat whole spinal cord was affected by TFP in a biphasic fashion, with an initial 25 and 65% enhancement of [3H]RTX binding, respectively, preceding inhibition. The apparent Ki values for inhibition were 3.93 +/- 0.13 microM for human dorsal horn and 7.91 +/- 0.62 microM for rat spinal cord. Scatchard analyses revealed that TFP affected both the affinity and the cooperativity of [3H]RTX binding by the receptors, leaving the receptor density unaltered. Similar effects on [3H]RTX binding to rat spinal cord membranes were also induced by other antipsychotic phenothiazines and other types of antipsychotics, by phenothiazines without antipsychotic actions, as well as by tricyclic antidepressants. In cultures of dorsal root ganglion neurones, TFP at concentrations that increased [3H]RTX binding (1-3 microM) also induced an increase in 45Ca uptake; this increase was absent in cultures prepared from capsaicin desensitized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Central vasopressin in experimental aortic stenosis in the rat.

OBJECTIVE: In several forms of heart disease characterised by low cardiac output, activated neurohumoral systems including increased vasopressin plasma levels play a key role in the changes in cardiovascular function. The aim of this study was to test the hypothesis that under such conditions the central vasopressin system might also be altered, which could contribute to deranged cardiovascular control. METHODS: Aortic stenosis was produced in 22 rats by placing a Silver clip (inner diameter 0.6 mm) on the ascending aorta. After 12 weeks, haemodynamic and hormonal measurements were performed, and vasopressin content was determined in 20 microdissected brain areas (micropunch technique). Twenty two sham operated rats served as controls. RESULTS: Twelve weeks after placing the supravalvular clip, significant aortic stenosis was documented by left ventricular myocardial hypertrophy. Cardiac index was significantly reduced and the peripheral vascular resistance index was increased, while poststenotic aortic pressure was non-significantly decreased. Plasma renin concentration [6.8(SEM 0.9) v 2.1(0.2) ngAI.ml-1.h-1 in controls] and plasma vasopressin [32.9(12.5) v 18.4(6.0) pg.ml-1] were significantly increased, while plasma and urinary noradrenaline remained unaltered. The vasopressin content was significantly altered in eight out of 20 brain areas investigated. Concerning the vasopressin producing hypothalamic nuclei, concentrations were increased in the paraventricular [7494(360) v 4744(237) pg.mg-1 protein, P < 0.05] and suprachiasmatic [3613(170) v 1784(197) pg.mg-1 protein, P < 0.01], but not in the supraoptic nuclei. Rats with aortic stenosis showed significantly raised vasopressin concentrations in the median eminence [25 186(1682) v 37 367(1345) pg.mg-1 protein, P < 0.01], where the hormone is mainly concentrated in the hypothalamo-hypophysial tract. Vasopressin content was significantly decreased in locus coeruleus [49(5) v 89(6) pg.mg-1 protein], which is known to be involved in modulation of sympathetic activity. CONCLUSIONS: As well as showing increased secretion of vasopressin into the blood with consecutive peripheral antidiuretic and vasoconstrictive effects, these data suggest an alteration in the central vasopressin system in aortic stenosis which might transmit cardiovascular effects by neuromodulation and neuroregulation.

Animals↗