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Biomedical subjects

M Brede

Publications and source records attributed to M Brede.

7 recordsLinked to original sources
PubMed2001

Vascular hypertrophy and increased P70S6 kinase in mice lacking the angiotensin II AT(2) receptor.

BACKGROUND: Angiotensin II activates 2 distinct G protein-coupled receptors, the AT(1) and AT(2) receptors. Most of the known cardiovascular effects of angiotensin II are mediated by the AT(1) receptor subtype. The aim of the present study was to test whether deletion of the AT(2) receptor gene in mice (AT(2)-KO mice) leads to long-term functional or structural alterations in the cardiovascular system. METHODS AND RESULTS: In vivo pressure responses to angiotensin II or the alpha(1)-adrenergic receptor agonist phenylephrine were greatly enhanced in AT(2)-KO mice. Deletion of the angiotensin AT(2) receptor did not lead to a compensatory increase of the activity of the circulating renin-angiotensin system, and arterial blood pressure was identical in wild-type control mice (WT) and AT(2)-KO mice. Cardiac contractility as assessed by LV catheterization and by rapid MRI also did not differ between AT(2)-KO and WT mice. Isolated femoral arteries from AT(2)-KO mice, however, showed enhanced vasoconstriction to angiotensin II, norepinephrine, and K(+) depolarization compared with WT. Morphometric analysis of large and small femoral arteries revealed a significant hypertrophy of media smooth muscle cells. Phospho-P70S6 kinase levels were significantly increased in aortas from AT(2)-KO mice compared with WT mice. Treatment of mice with an ACE inhibitor for 8 weeks abolished the increased pressure responsiveness, vascular hypertrophy, and enhanced P70S6 kinase phosphorylation in AT(2)-KO mice. CONCLUSIONS: These results indicate that vascular AT(2) receptors inhibit the activity and, hence, hypertrophic signaling by the P70S6 kinase in vivo and thus are important regulators of vascular structure and function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Architecture of idiotypic networks: percolation and scaling behavior.

We investigate a model where idiotypes (characterizing B lymphocytes and antibodies of an immune system) and anti-idiotypes are represented by complementary bit strings of a given length d allowing for a number of mismatches (matching rules). In this model, the vertices of the hypercube in dimension d represent the potential repertoire of idiotypes. A random set of (with probability p) occupied vertices corresponds to the expressed repertoire of idiotypes at a given moment. Vertices of this set linked by the above matching rules build random clusters. We give a structural and statistical characterization of these clusters, or in other words of the architecture of the idiotypic network. Increasing the probability p one finds at a critical p a percolation transition where for the first time a large connected graph occurs with probability 1. Increasing p further, there is a second transition above which the repertoire is complete in the sense that any newly introduced idiotype finds a complementary anti-idiotype. We introduce structural characteristics such as the mass distribution and the fragmentation rate for random clusters, and determine the scaling behavior of the cluster size distribution near the percolation transition, including finite size corrections. We find that slightly above the percolation transition the large connected cluster (the central part of the idiotypic network) consists typically of one highly connected part and a number of weakly connected constituents and coexists with a number of small, isolated clusters. This is in accordance with the picture of a central and a peripheral part of the idiotypic network and gives some support to idealized architectures of the central part used in recent dynamical mean field models.

Animals↗
PubMed2001

Transgenic mouse models of angiotensin receptor subtype function in the cardiovascular system.

Angiotensin II mediates is biological actions via different subtypes of G protein-coupled receptors, termed AT(1) and AT(2) receptors. In rodents, two AT(1) receptors have been identified, AT(1A) and AT(1B), whereas in humans a single AT(1) receptor exists. Recently, a number of transgenic animal models have been generated which overexpress or lack functional angiotensin II receptor subtypes. This review focuses on the physiological significance of angiotensin II receptor subtype diversity in the cardiovascular system. In the mouse, AT(1A) receptors are the major regulators of cardiovascular homeostasis by determining vascular tone and natriuresis. In addition, AT(1A) receptors mediate growth-stimulating signals in vascular and cardiac myocytes. AT(1B) receptors participate in blood pressure regulation, and their functions become apparent when the AT(1A) receptor gene is deleted. Deletion of the mouse gene for the AT(2) receptor subtype led to hypersensitivity to pressor and antinatriuretic effects of angiotensin II in vivo, suggesting that the AT(2) receptor subtype counteracts some of the biological effects of AT(1) receptor signalling.

Angiotensin II↗
PubMed1984

Influence of therapeutic phenobarbital and phenytoin medication on the polygraphic sleep of patients with epilepsy.

Sleep is a modulator of seizure activity, and many antiepileptic drugs are modulators of sleep. Can influences on sleep organization be involved in antiepileptic drug action, and can these partly account for differences in drug response of various epileptic syndromes? Much more exact data must be collected before these questions can be adequately discussed. The polygraphic sleep of 40 unmedicated epileptic patients was recorded and compared with polygraphy after adjustment to therapeutic steady states of phenobarbital (PB) and phenytoin (DPH) (as sequential sole agents in a crossover design with random sequence). With PB, patients fell asleep more rapidly and had fewer movements, movement arousals, and arousal awakenings, all of which could be beneficial, especially for patients with generalized epilepsy. Light sleep was increased, and REM sleep decreased. The usual sleep pattern was altered, with maximal deep sleep early and maximal REM sleep late in the night. PB seemed to have maximal effect in the first REM cycle. With DPH, sleep onset also came sooner, but light sleep was decreased and deep sleep increased, with no alteration of REM sleep. In contrast to PB, the changes in sleep organization were toward leveling the distribution of deep NREM sleep. The maximal alterations were observed in the third REM cycle. With both drugs, there were some differences in the response of generalized as opposed to focal epilepsies, and of awakening as opposed to sleep epilepsies. Thus, the early REM cycles seemed to be more modifiable by drugs in patients with generalized or awakening epilepsies than in patients with focal or sleep epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗