Influence of Nitric Oxide on Flow Mediated Dilation
Condition: FMD - Flow Mediated Dilation
MeSH terms: Dilatation, Pathologic
Study type: Observational

Summary: 
      Flow-mediated vasodilation (FMD) has become one of the most widely assessed parameter to
      analyze endothelial function. The peripheral endothelial function as assessed by FMD
      correlates with coronary artery endothelial function and moreover, impaired FMD has been
      revealed to be good predictor for cardiovascular events in patients beyond cardiovascular
      risk factors and in patients with coronary artery disease.

      This non-invasive technique measures the ability of the arteries to respond with endothelial
      release of vasoactive factors during reactive hyperemia. In this study the goal is to analyze
      in a clinical trial to what extend nitric oxide contribute to FMD by measuring FMD before and
      after blocking the release of nitric oxide. FMD is measured using a semi-automatic device
      named UNEX, recently developed in Japan. This semi-automatic ultrasound system represents a
      new development that overcomes the limitation of classic systems.

      The hypothesis of this study is that FMD response is mostly nitric oxide dependent. To prove
      this hypothesis, overall 20 healthy male volunteers are included in this study. Total
      duration of this study for each volunteer is 2-4 weeks with total 3 visits at the Clinical
      Research Unit (CRC) of the Department of Nephrology, University of Erlangen-Nuremberg.

      This study is important to better understand the mechanism of any kind of impaired FMD by
      cardiovascular risk factors and diseases and to better interpret impaired FMD assessed by
      UNEX.
    

Detailed description: 
      The assessment of endothelial function is crucial, as its dysfunction is described as a key
      pathological condition associated with many diseases leading to arteriosclerosis.
      Flow-mediated vasodilation (FMD) has become one of the most widely assessed parameter to
      analyze endothelial function. Celermajer et al. was the first to measure the FMD-response in
      vivo by ultrasound. This non-invasive technique measures the ability of the arteries to
      respond with endothelial release of vasoactive factors during reactive hyperemia.

      The peripheral endothelial function as assessed by FMD correlates with coronary artery
      endothelial function. Impaired FMD has been revealed to be good predictor for cardiovascular
      events in patients beyond cardiovascular risk factors and in patients with coronary artery
      disease. It is also predictive for the extent and severity of coronary atherosclerosis.

      Beyond the predictive nature of FMD, several studies have been reported on the effect of
      pharmacologic or physiologic interventions on FMD. For example weight loss and exercise
      increased FMD in overweight and obese patients with coronary heart disease.

      Impaired FMD is mainly characterized by reduced bioavailability of different vasodilators due
      to oxidative stress. Of these vasodilators nitric oxide plays the major role, but its
      contribution to FMD is inconclusive. Studies to clarify the role of nitric oxide on FMD have
      been done with various methods, which require extensive training and standardization.
      Operator, study preparation, image acquisition and site selection, sphygmomanometer probe
      position, cuff occlusion time, the accurate use of edge-detection software as well as the
      correct characterization of the FMD response are all factors, which influence FMD
      measurement.

      In this study the goal is to analyze in a clinical trial to what extent nitric oxide
      contribute to FMD by measuring FMD before and after blocking the release of nitric oxide. FMD
      is measured using a semi-automatic device named UNEX, recently developed in Japan. FMD
      measurements using UNEX implement the standards described in guidelines. This semi-automatic
      ultrasound system using an H-type ultrasound probe represents a new development that
      overcomes the limitation of classic systems (in particular the investigator-dependency of
      conventional, "hand-held" FMD measurements). This system comprised a 7.5-megahertz linear
      array transducer and a novel stereotactic probe-holding device (UNEX Co., Nagoya, Japan).
      Another advantage of this device is the continuous recording of B-mode images and A-mode
      waves of the artery in the longitudinal plane, so that continuous measurement of arterial
      diameter in the 4.5 min following cuff deflation occurs. A meta-analysis described that the
      nitric oxide dependency of the FMD response was the most in studies with FMD measurements at
      brachial artery with distal placement of the cuff and 5-minute occlusion. These criteria are
      fulfilled by UNEX. However, no data on nitric oxide dependency are available in the
      literature. Finally, this semi-automatic assessment of FMD has been shown to improve the
      precision and repeatability of the measurements.

      The hypothesis of this study is that FMD response is mostly nitric oxide dependent and this
      could not be proven so far due to less sensitive conventional tool of FMD measurement.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        -  Young, male and healthy volunteers without any significant disease

          -  Age of 18 and 45 years old
      
Keywords: nitric oxide