- Nitric Oxide and Endothelin Effects
- Neuropeptides and Animal Physiology
- Ion channel regulation and function
- Cardiac Ischemia and Reperfusion
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Receptor Mechanisms and Signaling
- Biosimilars and Bioanalytical Methods
- Cardiomyopathy and Myosin Studies
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Birth, Development, and Health
- Muscle activation and electromyography studies
- Migraine and Headache Studies
- Cardiac electrophysiology and arrhythmias
- Animal testing and alternatives
- Renin-Angiotensin System Studies
- Chemical Reaction Mechanisms
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- 3D Printing in Biomedical Research
- Heme Oxygenase-1 and Carbon Monoxide
- Apelin-related biomedical research
- Adenosine and Purinergic Signaling
- Paraquat toxicity studies and treatments
- Heart Rate Variability and Autonomic Control
Lundbeck (Denmark)
2023-2025
University of Copenhagen
2011-2016
Novo Nordisk (Denmark)
2002-2006
Université Libre de Bruxelles
2004
Maastricht University
1988-1994
Aarhus University
1993
The first Stakeholder Network Meeting of the EU Horizon 2020-funded ONTOX project was held on 13–14 March 2023, in Brussels, Belgium. discussion centred around identifying specific challenges, barriers and drivers relation to implementation non-animal new approach methodologies (NAMs) probabilistic risk assessment (PRA), order help address issues rank them according their associated level difficulty. aims advance chemical humans, without use animal testing, by developing NAMs PRA line with...
In activated rat mesenteric small arteries, the effect of pHi on force, membrane potential, and free cytosolic calcium ([Ca2+]i) was assessed. Arteries were mounted in a myograph for isometric force development, [Ca2+]i, pHi, or potential measured simultaneously with force. During activation norepinephrine, potassium, aluminum fluoride (AlF-4), phorbol 12-myristate 13-acetate (PMA, ester), vessels depolarized [Ca2+]i increased, although ratio to less during potassium than other types...
To evaluate long-term effects of contractile and mitogenic stimuli on the reactivity arterial smooth muscle, we measured incorporation thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) mechanical responses in segments that had been maintained tissue culture. The experiments were performed renal arteries isolated from adult rats, chemically sympathectomized, mechanically denuded endothelium mounted under distension. Exposure for up to 3 weeks culture medium supplemented with fetal calf...
6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives were synthesized and characterized as activators of adenosine 5'-triphosphate (ATP) sensitive potassium (K(ATP)) channels in the beta-cells by measuring effects on membrane potential insulin release vitro. The vascular tissue vitro measured rat aorta small mesenteric vessels. Selected compounds competitive inhibitors [(3)H]glibenclamide binding to membranes HEK293 cells expressing human SUR1/Kir6.2 potent...
Paraquat, an oxygen radical-generating agent, is a widely used agrochemical that also toxic for humans, in whom it may cause respiratory failure. In the present study, we investigated effect of deferoxamine (DF), iron chelator with antioxidant capacity, on paraquat toxicity vitamin E-deficient rats. After administration at dose 20 mg/kg animals were treated continuous intravenous infusion DF 14 days. dose-response four six receiving 100 mg DF/kg/24 h survived study period days compared none...
Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. inhibits insulin release in vitro and vivo preserves beta cell function preclinical animal models suggesting that such compound could find use treatment or prevention type 1 2 diabetes. The crystal structure convergent synthesis are presented together with range new analogues 1a. Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be openers...
Summary We evaluated whether chronic $$,-adrenergic stimulation, angiotensin II (All), or increased blood pressure (BP) alters resistance arterial structure and function. Structural parameters wall tension were recorded in mesenteric small arteries (MrA) isolated from 6-week-old normotensive Wistar Kyoto rats that had been infused for 4 days with saline (WKY), 2 mg/kg/day phenylephrine (WKY + PHE), 0.3 All ALL) saline-infused spontaneously hypertensive (SHR). During the experimental period,...
Abstract Mice are increasingly used in vascular research for studying perturbations and responses to vasoactive agents small artery preparations. Historically, function has preferably been studied rat isolated mesenteric resistance‐sized arteries ( MRA ) using the wire myograph technique. Although different mouse have no establishment of optimal settings yet performed. Therefore, purposes this study were firstly establish studies compare them those . Second, by surveying literature, we aimed...
To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated organoid culture a broad variety preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded endothelium, and suspended medium supplemented with serum. As judged nuclear incorporation thymidine analogue 5-bromo-2’-deoxyuridine (BrdUrd), this induced transient stimulation DNA synthesis only fraction smooth muscle cells...
We evaluated changes in DNA synthesis, structure, and mechanical activity isolated arteries during exposure to growth factors. Renal were from rats, sympathectomized, denuded of endothelium, maintained tissue culture. Up 4 days culture did not affect maximal contractile responses depolarization. From the results nuclear incorporation thymidine analogue 5-bromo-2-deoxyuridine (BrdUrd), stimulated synthesis. In media, BrdUrd was after 3 but fell precipitously thereafter. Culture arterial...
Angiotensin II (Ang II) might induce pro-inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim our study was to investigate putative direct and vasomotor Ang compare those lipopolysaccharides (LPS) mouse isolated mesenteric resistance-sized arteries (MRA) supported by experiments cultured human primary endothelial smooth muscle cells. Results showed that 24-hr organ culture MRA with 10 nM had, unlike 100 ng/mL LPS, no on IL-6 or MCP-1...
Phenylcyanoguanidines substituted with lipophilic electron-withdrawing functional groups, e.g. N-cyano-N'-[3,5-bis-(trifluoromethyl)phenyl]-N' '-(cyclopentyl)guanidine (10) and N-cyano-N'-(3,5-dichlorophenyl)-N' '-(3-methylbutyl)guanidine (12) were synthesized investigated for their ability to inhibit insulin release from beta cells, repolarize cell membrane potential, relax precontracted rat aorta rings. Structural modifications gave compounds, which selectively betaTC6 cells (e.g. compound...
The influence of ageing on the passive and active tension pharmacodynamic characteristics intramural coronary arteries from 3-month-old 2-year-old male Wistar rats was investigated using an isometric myograph. vessel wall measured in Ca2+-free physiological salt solution at L₀ significantly greater old (1.46 ± 0.10 Nm–1, n = 7) than young (1.13 0.13 6). However, maximal similar. spontaneous myogenic tone increased by age vasorelaxation induced extracellular K+ higher rats. sensitivity (pD2)...
We compared the distribution of DNA synthesis over arterial tree young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive (SHR) with marginally elevated blood pressure. Six-week-old male SHR WKY were therefore infused 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days nuclear incorporation thymidine analogue in media various arteries was determined by immunohistochemistry. In rats, 2.5% smooth muscle nuclei elastic, muscular resistance incorporated BrdUrd. SHR, more marked large...
We evaluated effects of the β-adrenoceptor antagonist tertatolol on responses resistance arteries to isoproterenol and phenylephrine compared them with those propranolol. The experiments were performed in femoral, mesenteric, renal that had been isolated from adult Wistar-Kyoto rats, chemically sympathectomized mounted for recording contractile reactivity vitro. In pretreated phenoxybenzamine, did not affect potassium. Under these conditions, induced relaxation mesenteric arteries. Low...
Obesity is an increasing burden affecting developed and emerging societies since it associated with increased risk of diabetes consequent cardiovascular complications. Increasing evidence points towards a pivotal role inflammation in the etiology vascular dysfunction. Our study aimed to investigate signs their relation dysfunction rats receiving high fat diet.Diet-induced obese (DIO) were used as model these exhibit human pre-diabetic pathology. Oral glucose insulin tolerance tests conducted...