Vascular Dysfunction in Hypertensive Postmenopausal Women
Condition: Cardiovascular Diseases; Hypertension
MeSH terms: Hypertension; Cardiovascular Diseases
Intervention: Normotensive; Hypertensives
Intervention description: FMD is a measure of endothelial function by assessing the degree to which vessel dilates in response to increased flow. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection in all women. Laser Doppler flowmetry is used in combination with cutaneous microdialysis as a minimally invasive technique to examine mechanisms of vascular function. ET-B and ET-A receptor antagonists will be perfused via intradermal microdialysis fibers while measuring cutaneous blood flow. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will also be assessed. Immunohistochemistry will be performed on skin punch biopsy samples to assess for protein expression of ET-A and ET-B receptors.; ANG II increases the synthesis of ET-1 and alters ET-A/B receptor expression, thus affecting ET-1 bioavailability. Losartan is an ANG II receptor antagonist which attenuates ET-1 production. Losartan 50 mg daily is administered for 14 days to hypertensive women. FMD is used to measure endothelial function. Pulse Wave Analysis and Pulse Wave Velocity assesses arterial stiffness and wave reflection. Laser Doppler flowmetry with cutaneous microdialysis is used to examine vascular function when ET-A and ET-B receptor antagonists is perfused via intradermal microdialysis fibers. ET-1 production and ET-B receptor expression in endothelial cells collected from an antecubital vein will be assessed. Skin punch biopsy samples will be used to assess for protein expression of ET-A and ET-B receptors.
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: Female
Minimum age: 50 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hypertension; Endothelin-1 receptor

Summary:

      The purpose of this study is to investigate the role of ET-1 in mediating vasoconstrictor
      tone in hypertensive postmenopausal women (PMW) alone and in combination with a commonly
      prescribed Angiotensin II (ANG II) antagonist. The long term goal is to understand the
      mechanisms contributing to hypertension (HTN) in PMW. This study is the first step in
      reaching our goal.
    

Eligibility criteria:

        Inclusion Criteria: - Women.

          -  > 1year post menopausal.

          -  Age range 50-70 years

          -  Resting ECG in normal limits

          -  Standard blood chemistry within normal limits

          -  Systolic blood pressure: <130mm Hg for normotensives; >130mm Hg for hypertensives.

          -  Diastolic blood pressure: < 80mm Hg for normotensives; > 80mm Hg for hypertensives.

        Exclusion Criteria:

          -  History of cardiovascular disease

          -  Blood clots or stroke

          -  Cancer

          -  Diabetes

          -  Kidney or Liver disease

          -  Obesity (BMI>35kg/m2)

          -  Pregnant/Breast feeding

          -  Current use of hormone therapy

          -  Current use of tobacco products

          -  High cholesterol

          -  Current use of anti-hypertensive meds