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W Häuser

Publications and source records attributed to W Häuser.

At least 55 records · Page 3Linked to original sources
PubMed1999

Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation.

The hippocampal formation of Mongolian gerbils expresses high amounts of atypical angiotensin II type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific [35S]-labeled riboprobes and by receptor autoradiography using [125I]Sarcosine1-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidal cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfields, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression.

Animals↗
PubMed1999

Centrally bradykinin B2-receptor-induced hypertensive and positive chronotropic effects are mediated via activation of the sympathetic nervous system.

OBJECTIVE: The presence of bradykinin B2 receptors in the cardiovascular regulatory centres of the brain indicates that increase in mean arterial pressure (MAP) and heart rate after intracerebroventricular (i.c.v.) injections of bradykinin is mediated via stimulation of sympathetic nervous system. METHODS: Adult Wistar- Kyoto (WKY) rats were instrumented chronically with an i.c.v. cannula, and the catheters were placed into the femoral artery and vein. Increasing doses of bradykinin (1 -300 pmol) were given i.c.v. and (i) MAP and heart rate, (ii) plasma dopamine, noradrenaline and adrenaline, and (iii) plasma arginine vasopressin (AVP) levels were determined. In addition, following blockade of peripheral alpha1 -adrenoceptors with prazosin (50 and 250 microg/kg i.v.) beta1-adrenoceptors with atenolol (10 mg/kg i.v.) or V1 -receptors with TMe-AVP (Manning compound) (10 microg/kg i.c.v. and 100 microg/kg i.v.) the effects of bradykinin (100 pmol i.c.v.) on MAP and heart rate were determined. RESULTS: Bradykinin increased MAP and heart rate dose-dependently. The pressor effects of 100 pmol bradykinin i.c.v. were completely blocked by pretreatment with the specific B2 receptor antagonist Hoe 140 (3 pmol, i.c.v.). There was no change in plasma dopamine, noradrenaline, adrenaline or AVP levels after increasing doses of bradykinin. However, peripheral blockade of alpha1- and beta1-adrenoceptors reduced the bradykinin-induced increase in MAP and heart rate, whereas central and peripheral V1 receptor blockade did not alter the cardiovascular responses to i.c.v. bradykinin. CONCLUSION: Our data suggest that the hypertensive and positive chronotropic effects induced by i.c.v. bradykinin are due to stimulation of sympathoneuronal rather than sympathoadrenal pathway in vivo.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

[Four minutes for the patient and one minute for the families. Physician-patient-family communication in medical departments].

Facing the changes in working situation of hospital doctors, the question is raised as show how much time is spent on communication with patients and their families. The daily working time, including the time spent on communication with patients and their families, of 24 ward doctors (junior and senior house officers) from 5 medical departments at general hospitals, were assessed by means of questionnaires and time measurements. An average daily working time of 8.6 hours, yielding an average of 4 minutes for communication with each patient and 1 minute with his family.

Adult↗
PubMed1998

Chemical lesion of the inferior olive reduces [125I]sarcosine1-angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats.

In young rats, AT2 receptors and AT2 receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT2 receptor binding, but not AT2 receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT2 receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [125I]Sar1-Ang II binding to AT2 receptors and AT2 receptor mRNA levels in this area by 50%, and produced a similar decrease in AT2 receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [125I]Sar1-Ang II binding to AT1 receptors in the molecular layer of the cerebellar cortex or AT1 receptor mRNA levels in Purkinje cells. AT2 receptor binding and AT2 receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT2 receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT2 receptors in the inferior olivary-cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT2 receptors in the development of this pathway.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1998

Characterization and distribution of angiotensin II receptor subtypes in the mouse brain.

We localized and characterized angiotensin II receptor subtypes (AT1 and AT2) in the mouse brain, with the use of autoradiography after incubation with [l25I][Sar1]-angiotensin II or [125I]CGP 42112 and displacement with selective angiotensin AT1 (losartan and candesartan) or angiotensin AT2 (CGP 42112(1) and PD 123319(2)) receptor ligands. In the mouse, the receptor subtype affinity for the different ligands was similar to that of the rat. The receptor subtype distribution was also similar to that in the rat, with some notable exceptions, such as the presence of angiotensin AT1 but not AT2 receptors in the locus coeruleus, and the expression of angiotensin AT1 receptors in the caudate putamen. These results confirm that careful consideration of the specific distribution of receptor subtypes in different species, even those closely related such as the mouse and the rat, should be conducted before meaningful comparisons could be proposed. Our data also form the basis for future studies of mouse models such as those with angiotensin receptor gene deficiencies.

Angiotensin II↗
PubMed1998

The angiotensin AT1 receptor antagonist CV-11974 regulates cerebral blood flow and brain angiotensin AT1 receptor expression.

We studied cerebral blood flow autoregulation by laser Doppler flowmetry, and expression of brain angiotensin II AT1 receptors by quantitative autoradiography, after administration of an angiotensin AT1 receptor antagonist, CV-11974 (Candesartan, 0.5 or 1.0 mg/kg.day) for two weeks via subcutaneously implanted osmotic pumps in adult normotensive Wistar Kyoto and spontaneously hypertensive male rats (SHR). In SHR, the autoregulation curve was shifted towards higher blood pressures, when compared with that of normotensive Wistar Kyoto rats. Administration of CV-11974 shifted the autoregulation curve toward lower blood pressures in both Wistar Kyoto and SHR, partially normalizing the autoregulation curve in SHR. CV-11974 treatment markedly decreased the expression of AT1 receptors in Wistar Kyoto rats, both in areas outside the blood brain barrier (subfornical organ, 95% decrease) and inside the blood brain barrier (nucleus of the tractus solitarius, 87% decrease, and paraventricular nucleus, 96% decrease). Our results demonstrate that blockade of AT1 receptors tends to normalize the shift to higher pressures in the autoregulation curve of genetically hypertensive rats, and has a profound modulatory role in brain angiotensin II AT1 receptors.

Angiotensin Receptor Antagonists↗
PubMed1998

Effects of the AT1 antagonist HR 720 in comparison to losartan on stimulated sympathetic outflow, blood pressure, and heart rate in pithed spontaneously hypertensive rats.

It has been demonstrated in isolated organs that angiotensin II mediates catecholamine release via presynaptically located AT1 receptor subtypes. In the present study, the relevance of AT1-mediated noradrenaline and adrenaline release in a whole-animal model, which reflects the peripherally sympathetic system (pithed rat), was investigated. Furthermore, the effects of a new AT1 antagonist, HR 720, are demonstrated with respect to its pre- and postsynaptic actions in comparison to the AT1 antagonist losartan. Dose-response curves to angiotensin II of blood pressure show a tenfold higher potency for HR 720 to compete for angiotensin II, thereby decreasing the maximum effects when compared with losartan. The electrically induced sympathetic outflow resulted in a dose-dependent increase after angiotensin II infusions. It could markedly be reduced with both AT1 antagonists, whereby HR 720 again was ten times more potent than losartan. Neither with HR 720 nor with losartan an agonistic activity could be demonstrated. The results indicate an AT1 receptor subtype mediated release of catecholamines in a whole-animal model. HR 720 is ten times more potent than the AT1 antagonist losartan and acts in a noncompetitive manner.

Angiotensin I↗
PubMed1997

Localization of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor subtypes, and vasopressin in the mouse hypothalamus.

The hypothalamic angiotensin II (Ang II) system plays an important role in pituitary hormone release. Little is known about this system in the mouse brain. We studied the distribution of angiotensin-converting-enzyme (ACE), Ang II, Ang II receptor subtypes, and vasopressin in the hypothalamus of adult male mice. Autoradiography of binding of the ACE inhibitor [125I]351A revealed low levels of ACE throughout the hypothalamus. Ang II- and vasopressin-immunoreactive neurons and fibers were detected in the paraventricular, accessory magnocellulary, and supraoptic nuclei, in the retrochiasmatic part of the supraoptic nucleus and in the median eminence. Autoradiography of Ang II receptors was performed using [125I]Sar1-Ang II binding. Ang II receptors were present in the paraventricular, suprachiasmatic, arcuate and dorsomedial nuclei, and in the median eminence. In all areas [125I]Sar1-Ang II binding was displaced by the AT1 receptor antagonist losartan, indicating the presence of AT1 receptors. In the paraventricular nucleus [125I]Sar1-Ang II binding was displaced by Ang II (Ki = 7.6 X 10(-9)) and losartan (Ki = 1.4 X 10(-7)) but also by the AT2 receptor ligand PD 123319 (Ki = 5.0 X 10(-7)). In addition, a low amount of AT2 receptor binding was detected in the paraventricular nucleus using [125I]CGP42112 as radioligand, and the binding was displaced by Ang II (Ki = 2.4 X 10(-9)), CGP42112 (Ki = 7.9 x 10(-10)), and PD123319 (Ki = 2.2 x 10(-7)). ACE, Ang II, and AT1 as well as AT2 receptor subtypes are present in the mouse hypothalamus. Our data are the basis for further studies on the mouse brain Ang II system.

Angiotensin II↗
PubMed1997

[Pain management in patients with chronic rheumatic pain--a model for primary medical care].

A rheumatologist and a medical psychotherapist collaborate in offering periodically a cognitive behavioral treatment program for pain control for the patients of a rheumatological practice. The program consists of a biopsychosocial model of chronic pain, individualized relaxation training combining progressive muscle relaxation and some elements of autogenous training and meditation, several attention-related techniques and cognitive restructuring. From 1993 to 1995, 50 patients took part in five training courses. The compliance of the patients was satisfactory and the drop-out rate low (8%). In a post hoc interview 4 weeks later and another 2 years after the end of the training most of the patients assessed the program as useful for reduction of pain, increase of activity and enhancement of mood. Psychotherapeutic experience in group therapy or special training for non-psychotherapeutic physicians with continuous supervision is necessary in order to conduct a qualified treatment program. Within medical primary care, rheumatologists can motivate their patients towards active pain management, which can help to prepare patients for further psychotherapy in cases with psychiatric disorders and/or severe psychosocial strains.

English Abstract↗
PubMed1997

Water deprivation upregulates ANG II AT1 binding and mRNA in rat subfornical organ and anterior pituitary.

We studied angiotensin II (ANG II) receptor subtype expression in selected brain nuclei and pituitary gland after water deprivation by in vitro receptor autoradiography using 125I-labeled [Sar1]ANG II and by in situ hybridization using 35S-labeled AT1A, AT1B, and AT2 receptor-specific riboprobes. In control rats we found binding to AT1 receptors in the subfornical organ, paraventricular nucleus, median eminence, and anterior pituitary; AT1A mRNA expression in the subfornical organ and paraventricular nucleus; and AT1B mRNA expression in the anterior pituitary. No receptor mRNA was found in the median eminence. AT1 receptors and AT1A receptor mRNA levels were increased in the subfornical organ, and, in the anterior pituitary, AT1 receptors and AT1B receptor mRNA were increased, only after 5 days of water deprivation. No significant changes occurred after 1 or 3 days of water deprivation, and no regulation of ANG II receptor expression was detected in other brain areas. Our results show that prolonged water deprivation selectively regulates AT1 receptor expression and AT1A and AT1B receptor mRNA levels in the subfornical organ and anterior pituitary, respectively, supporting a role for these receptors during sustained dehydration.

Animals↗
PubMed1996

Effects of angiotensin converting enzyme inhibitor on renal haemodynamics during mental stress.

OBJECTIVE: To examine the effects of angiotensin converting enzyme (ACE) inhibition on renal and systemic haemodynamics as well as on humoral regulators, under resting conditions and during mental stress in 20 normotensive and 20 mildly hypertensive subjects. METHODS: All of the subjects received either 25 mg cilazapril or placebo once a day, in a randomized, double-blind, cross-over trial for 1 week, followed by a 2-week washout period before the alternative regimen was given. We measured renal blood flow with para-aminohippuran, glomerular filtration rate with inulin, cardiac output by impedance cardiography and blood pressure and heart rate by an oscillometric method. We also monitored effects on plasma renin activity, aldosterone, catecholamines and atrial natriuretic peptide. Mental stress consisted of a long-lasting, time-reaction device, thereby provoking activation of the sympathetic nervous system. RESULTS: At rest ACE inhibition lowered mean arterial pressure (92 +/- 10 versus 98 +/- 9 mmHg), increased renal blood flow (803 +/- 109 versus 707 +/- 93 ml/min) and the renal fraction of cardiac output (25.9 +/- 2.5 versus 23.5 +/- 2.5%) and decreased the filtration fraction (17.9 +/- 2.5 versus 19.8 +/- 2.7%) in hypertensive but not in normotensive subjects. Sympathetic activation by mental stress leading to a transient increase in blood pressure did not alter significantly the effects of ACE inhibition on renal and systemic haemodynamics, in normotensive or in hypertensive subjects, although a tendency towards attenuation of the rise in glomerular filtration rate was noted in hypertensives (7.2 +/- 1.0 versus 5.1 +/- 0.8%). ACE inhibition led to increased plasma noradrenaline at rest but not during mental stress in hypertensive patients. CONCLUSION: ACE inhibition in patients with mild hypertension increased selectively renal perfusion, which is conserved during mental stress without persistent effects on the sympathetic nervous system. Thus, mental stress as a correlate of daily life stress appeared not to confound the selective renal vasodilatory effect of ACE inhibitors.

Adult↗
PubMed1996

Bradykinin increases catecholamine release via B2 receptors.

The mechanism by which bradykinin induces catecholamine release from neural tissues was investigated in two experimental models of rat origin. The rat phaeochromocytoma cell line PC12 was used to identify the subtype of bradykinin receptors involved in the stimulation of noradrenaline secretion and to compare the effects of three different B2-antagonists. An increase of catecholamine release induced by bradykinin in vivo could be confirmed by measuring plasma levels in pithed spontaneously hypertensive rats (SHR) during electric preganglionic stimulation of the spinal cord. In this whole animal model, the effects of inhibition of both uptake and alpha 2-adrenoceptors on plasma levels of noradrenaline and adrenaline were studied as well as the potentiation of exogenous bradykinin by inhibition of angiotensin I-converting enzyme and neutral endopeptidase. The receptor subtypes involved (i.e. B1 or B2) were characterized by application either of HOE 140 or desArg9-[Leu8]-bradykinin respectively. In PC12 cells bradykinin provoked a prominent increase of noradrenaline release at low concentrations (concentration required for 50% of the maximum response 1 nM), whereas the B1-agonist desArg9-bradykinin was only effective at concentrations higher than 30 microM. The effects of both kinins could be blocked by the B2-specific antagonist HOE 890307 which, like HOE 140, exerted no agonistic effect of its own. As has been shown in other neural cells, the B2-specific antagonist [Thi5,8, D-Phe7]-bradykinin only acted as a low-affinity agonist without any antagonistic effects. In experiments where the intention was to induce B1-receptor expression either by angiotensin I-converting enzyme inhibition or lipopolysaccharide application, no alteration of the secretory response of PC12 cells to bradykinin or desArg9-bradykinin could be shown. In pithed SHR, infusion of bradykinin (up to 1200 ng/min/kg) did not enhance stimulation-dependent release of noradrenaline or adrenaline. After pretreatment of the rats with ramipril bradykinin became effective and its effects were further potentiated by the concomitant application of phosphoramidon. B2-antagonism by HOE 140 abolished the bradykinin-induced release of noradrenaline and reduced the effect on plasma adrenaline. The B1-specific antagonist desArg9-[Leu8]-bradykinin was unable to diminish the stimulatory effects of bradykinin and instead brought about an increase of plasma adrenaline levels. In conclusion, bradykinin stimulates release of catecholamines from PC12 cells, peripheral sympathetic neurons and chromaffine cells by activation of ganglionic or presynaptic B2-receptors. The adrenal medulla and PC12 cells appear to be highly susceptible not only to stimulation by bradykinin, but also to non-specific stimulatory effects of certain kinin-antagonists.

Acetylcholine↗
PubMed1995

Influence of imidazolines on catecholamine release in pithed spontaneously hypertensive rats.

The actions of the imidazoline derivatives clonidine, moxonidine, and rilmenidine and of the recently discovered clonidine-displacing substance agmatine on stimulation-induced norepinephrine overflow and epinephrine release were studied in pithed spontaneously hypertensive rats. All three imidazolines dose-dependently decreased norepinephrine overflow and led to an increase in epinephrine release when the highest dose of each compound was injected. The alpha 2-adrenoceptor antagonist rauwolscine shifted the dose-response curves of plasma norepinephrine concentrations to higher levels. Agmatine did not change norepinephrine overflow but increased epinephrine release into plasma after the highest dose administered. It is concluded that the investigated imidazolines decrease norepinephrine overflow via presynaptic alpha 2-adrenoceptors, whereas epinephrine release is mediated through putative imidazoline receptors on the adrenal medulla.

Agmatine↗
PubMed1990

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Quality of life assessment in Inflammatory Bowel Disease (IBD): German version of the Inflammatory Bowel Disease Questionnaire (IBDQ-D; disease-specific instrument for quality of life assessment) -- first application and comparison with international investigations].

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome-parameter in health research and care. The aim of the working group Quality of Life in the Competence Network Inflammatory Bowel Disease (IBD; in the original German: "Kompetenznetz chronisch entzündliche Darmerkrankungen") is to generate instruments for assessment of HRQOL and its implementation as standards in clinical trials, health care and research in IBD. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ) is an international validated disease specific instrument for HRQOL-assessment. A German version of the IBDQ was elaborated and tested in 415 outpatients with Crohn's disease (CD, n = 306) and ulcerative colitis (UC, n = 109). The aim of the study was to compare the results of HRQOL-assessment (IBDQ-D) with international investigations, to correlate HRQOL results with disease activity and to preform a pretest of psychometric properties. RESULTS: International data suggest that the IBDQ-D is a suitable instrument for HRQOL-assessment in CD and UC. For both disease a statistically significant negative correlation with disease activity was found. Tested psychometric properties do not suggest that a revision of the IBDQ-D is required. The IBDQ-D offers the HRQOL-assessment as an primary or secondary outcome in clinical trials in IBD in Germany.

Adult↗