Ulf Simonsen

Research

Pulmonary and Cardiovascular Pharmacology
The research group aims to develop novel pharmacological approaches to improve endothelial function in cardiovascular disease. Endothelial cell function and signal transduction is investigated under normal and pathophysiological conditions both in collaboration with basic science as well as clinical departments. Endothelial dysfunction is also linking cardiovascular disease to erectile dysfunction, and plays an important role in the development of pulmonary hypertension.

Research interests

Endothelial Dysfunction
This is defined by decreased endothelium-dependent vasodilatation, and is associated with an increased number of cardiovascular events. The research group aim to develop novel pharmacological approaches to improve endothelial function in cardiovascular disease. Endothelial cell function and signal transduction is investigated under normal and pathophysiological conditions both in collaboration with basic science as well as clinical departments.

Pharmacological Treatment of Pulmonary Hypertension caused by hypoxia or fibrosis
Pulmonary hypertension is a life-threatening disease characterized by abnormal pulmonary vasoconstriction, proliferation of the cells in the vascular wall, progressive lung fibrosis, and is followed by right ventricular hypertrophy and failure. Despite an intense research activity and development of new drugs, the present treatments are not able to prevent progression of pulmonary hypertension in patients with pulmonary disease e.g. chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). The project is translational and  performed within the Centre for Vascular Pulmonary Hypertension which is focused at improving diagnosis and treatment of patients suffering from pulmonary hypertension, and is a collaboration in between Institute of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University and the Departments of Pulmonology and Cardiology, Aarhus University Hospital. In recent prevalence studies in patients with COPD and ILD, we have found that 10-15% of the patients have pulmonary hypertension, and that the disease is severely affecting survival. In proteomic and microarray studies performed in hypoxic cells and animals  with experimental pulmonary hypertension we have found that endothelial cation channels  as well as other proteins play an important role in the disease. The overall aim is to develop treatments of pulmonary hypertension by targetting the involved signal pathways.

Pharmacological Treatment of Erectile Dysfunction
Phosphodiesterase type 5 inhibitors, e.g. sildenafil (Viagra R ) are efficient in the treatment of most cases of erectile dysfunction, but less so in patients with erectile dysfunction and diabetes. Therefore, novel pharmacological approaches are required for the treatment of erectile dysfunction associated with diabetes.

Methodologies

  • Examination of structure and function in small arteries in vitro
  • Measurements of contractility, membrane potential, cytoplasmic ion concentrations, protein expression, protein phosphorylation, morphological measurements
  • Measurements of nitric oxide concentration
  • Electrochemical nano-and microsensors are applied for simultaneous measurements of nitric oxide and contractility. Nitrite concentrations estimated by chemiluminescence e.g. Sievers.
  • Cell culture studies
  • Endothelial cells and vascular smooth muscle cells are cultured to elucidate molecular mechanisms underlying effects of drugs.
  • In vivo measurements of pulmonary and systemic blood pressure in rodents
  • Right ventricular pressure and systemic blood pressure are measured by use of Millar catheters and DSI telemetric pressure transducers for rats and mice including transgenic animals.
  • In vivo measurements of lung function in rodents
  • By use of Flexivent equipment lung function is evaluated in rats and mice with pulmonary disease.
  • In vivo measurements of erectile function in rodents

Collaborators and centres

Collaborators:

  • Prof. Alun Hughes, Department of Clinical Pharmacology, Imperial College, London
  • Senior Scientist Ralf Köhler, CNIC Research Centre, Zaragoza, Spain
  • Prof. Luis Rivera, Department of Physiology, Complutense University, Spain

Centres:

  • The research group form part of the Center on Pharmacotherapy, Department of Biomedicine, Aarhus University
  • The research group form part of the Center on Pulmonary Vascular Disease at Aarhus University Hospital

Research group members

Moreover, the group supervises a number of research year students, master student,  and exchange  students.

Group leader

Ulf Simonsen

Professor
M
H bldg. 1242, 341
P +4587167685
P +4560202613

Publications

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