A5056794023- Hormonal Regulation and Hypertension
- Renin-Angiotensin System Studies
- Sodium Intake and Health
- Blood Pressure and Hypertension Studies
- Heart Rate Variability and Autonomic Control
- Renal function and acid-base balance
- Receptor Mechanisms and Signaling
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Ion Transport and Channel Regulation
- Diet and metabolism studies
- Electrolyte and hormonal disorders
- Eicosanoids and Hypertension Pharmacology
- Antibiotics Pharmacokinetics and Efficacy
- Nitric Oxide and Endothelin Effects
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiovascular Syncope and Autonomic Disorders
- Adipose Tissue and Metabolism
- Vasculitis and related conditions
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Renal and Vascular Pathologies
- Heart Failure Treatment and Management
- Reproductive System and Pregnancy
- Cardiovascular and exercise physiology
Max Delbrück Center
2015-2024
Charité - Universitätsmedizin Berlin
2015-2024
Freie Universität Berlin
1999-2024
Humboldt-Universität zu Berlin
2001-2024
Heidelberg University
1987-2024
University Hospital Heidelberg
2000-2024
Duke-NUS Medical School
2024
National Heart Centre Singapore
2024
Linde (Germany)
2011-2022
Vanderbilt University
2006-2018
Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component caveolae, we generated mice lacked caveolae. The absence this organelle impaired nitric oxide calcium signaling cardiovascular system, causing aberrations endothelium-dependent relaxation, contractility, maintenance myogenic tone. In addition, lungs knockout animals...
Antibodies against HLA antigens cause refractory allograft rejection with vasculopathy in some, but not all, patients.We studied 33 kidney-transplant recipients who had vascular rejection. Thirteen donor-specific anti-HLA antibodies, whereas 20 did not. Malignant hypertension was present 16 of the patients without 4 whom seizures. The remaining 17 no malignant hypertension. We hypothesized that activating antibodies targeting angiotensin II type 1 (AT1) receptor might be involved.Activating...
Immune mechanisms and the renin–angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients compared them with 12 normotensive pregnant women 10 essential hypertension. Antibodies were detected by chronotropic responses to AT1 receptor–mediated stimulation of cultured neonatal rat cardiomyocytes coupled receptor-specific antagonists. Immunoglobulin from all stimulated receptor, whereas immunoglobulin controls had no effect. The increased autoimmune activity...
Sensitivity and resistance to the effects of sodium were evaluated in normotensive hypertensive humans by two approaches. Blood pressure was measured after an intravenous infusion 2 L normal (0.9%) saline volume depletion induced a low diet furosemide administration 378 volunteers 198 subjects with essential hypertension. Those whom mean arterial blood decreased at least 10 mm Hg considered sodium-sensitive, those decrease 5 or less (including increase pressure) sodium-resistant. The second...
Obesity is the main risk factor for development of type 2 diabetes. Activation central endocannabinoid system increases food intake and promotes weight gain. Blockade cannabinoid 1 (CB-1) receptor reduces body in animals by peripheral actions; role human obesity now being extensively investigated. We measured circulating concentrations studied expression CB-1 degrading enzyme, fatty acid amide hydrolase (FAAH), adipose tissue lean (n = 20) obese women after a 5% loss second group 17)....
The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on circulating adipose tissue menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, angiotensin II. In biopsy samples, we renin-receptor, enzyme, II type-1 receptor gene expression. Obese women (n=19) had higher than lean (n=19), lower angiotensinogen...
The course of tissue changes in acute myocarditis humans is not well understood. Diagnostic tools currently available are unsatisfactory. We tested the hypothesis that inflammation reflected by signal contrast-enhanced magnetic resonance imaging (MRI).We assessed 44 consecutive patients with symptoms myocarditis. Nineteen met inclusion criteria revealing ECG changes, reduced myocardial function, elevated creatine kinase, positive troponin T, serological evidence for viral infection,...
Among the TRPC subfamily of TRP (classical transient receptor potential) channels, TRPC3, -6, and -7 are gated by signal transduction pathways that activate C-type phospholipases as well direct exposure to diacylglycerols. Since TRPC6 is highly expressed in pulmonary vascular smooth muscle cells, it represents a likely molecular candidate for receptor-operated cation entry. To define physiological role TRPC6, we have developed TRPC6-deficient mouse model. These mice showed an elevated blood...
Virtually all blood vessels are surrounded by adventitial fat. Adipocytes produce a host of vasoactive substances that may influence vascular contraction. We tested whether or not perivascular adipose tissue modulates contraction aortic ring preparations. studied rings periadventitial from adult Sprague-Dawley rats. At maximum concentration 300 nM angiotensin II, 6.5 microM serotonin, and 5 phenylephrine, the contractile response intact was 95%, 80%, 30% lower than without The...
Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate relationship between adiponectin, gene expression in adipose tissue, markers inflammation, we obtained blood samples, anthropometric measures, subcutaneous tissue samples from 65 postmenopausal healthy women. Adiponectin adipose-tissue were significantly lower obese subjects inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein...
In animals, electric field stimulation of carotid baroreceptors elicits a depressor response through sympathetic inhibition. We tested the hypothesis that acutely reduces vasomotor tone and blood pressure in patients with drug treatment-resistant arterial hypertension. Furthermore, we whether impairs physiological baroreflex regulation. studied 7 men 5 women (ages 43 to 69 years) A bilateral stimulator at level sinus (Rheos) was implanted > or =1 month before study. measured intra-arterial...
Abstract —We recently reported that the activation of nuclear factor-κB (NF-κB) promotes inflammation in rats harboring both human renin and angiotensinogen genes (double-transgenic [dTGR]). We tested hypothesis antioxidant pyrrolidine dithiocarbamate (PDTC) inhibits NF-κB ameliorates renal cardiac end-organ damage. dTGR feature hypertension, severe damage, a 40% mortality rate at 7 weeks. Electrophoretic mobility shift assay showed increased DNA binding activity hearts kidneys dTGR. Chronic...
Most renal transplants fail because of chronic allograft nephropathy or the recipient dies, but no reliable factor predicting long-term outcome has been identified. We tested whether a arterial resistance index less than 80 was predictive survival.The segmental (the percentage reduction end-diastolic flow as compared with systolic flow) measured by Doppler ultrasonography in 601 patients at least three months after transplantation between August 1997 and November 1998. All were followed for...
Anti-neutrophil cytoplasmic autoantibody (ANCA)-induced necrotizing crescentic glomerulonephritis (NCGN) requires complement participation in its pathogenesis. We tested the hypothesis that anaphylatoxin C5a is pivotal to disease induction via neutrophil receptor (C5aR). Supernatants from ANCA-activated neutrophils activated cascade normal serum, producing C5a. This conditioned serum primed for ANCA-induced respiratory burst; C5aR blockade abrogated this priming, but C3aR did not....
The skin interstitium sequesters excess Na+ and Cl- in salt-sensitive hypertension. Mononuclear phagocyte system (MPS) cells are recruited to the skin, sense hypertonic electrolyte accumulation activate tonicity-responsive enhancer-binding protein (TONEBP, also known as NFAT5) initiate expression secretion of VEGFC, which enhances clearance via cutaneous lymph vessels increases eNOS blood vessels. It is unclear whether this local MPS response osmotic stress important systemic pressure...
High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases age. We hypothesized that tissue Na + might accumulate in hypertensive patients and aging be accompanied by deposition tissue. implemented 23 magnetic resonance imaging to measure content soft tissues vivo earlier, but had not studied essential hypertension. report on a cohort 56 healthy control men women, 57 women The ages ranged from 22 90 years. measurements were made at level...
Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated humans. RBP4 was highly expressed isolated mature human secreted by differentiating adipocytes. In contrast to the animal data, mRNA downregulated subcutaneous adipose tissue obese women, circulating concentrations were similar normal weight, overweight, women (n = 74). positively correlated with GLUT4...
Eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) protect against cardiovascular disease by largely unknown mechanisms. We tested the hypothesis that EPA DHA may compete with arachidonic (AA) for conversion cytochrome P450 (CYP) enzymes, resulting in formation of alternative, physiologically active, metabolites. Renal hepatic microsomes, as well various CYP isoforms, displayed equal or elevated activities when metabolizing instead AA. CYP2C/2J isoforms converting AA to...