The Role of Aldosterone on Augmented Exercise Pressor Reflex in Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Eplerenone; Amlodipine; Microneurography; Rhythmic handgrip exercise; Sustained hand grip; Forearm blood flow; Arm cycling exercise; Cold Pressor test
Intervention description: The subject will be started on Eplerenone (Inspra) 50-200mg daily, which he or she will continue for a period of 8 weeks. Following the 8-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued; The subject will be started on Amlodipine (Norvasc) 2.5 -10mg daily, which he or she will continue for a period of 8 weeks. Following the 8-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.; Investigators will measure sympathetic nerve activity from the peroneal nerve by inserting a tiny needle directly into the nerve in the leg. Investigators will localize the nerve by electrical stimulation over the skin using a blunt probe. With this stimulation, subject will notice either involuntary twitching or a tingling sensation, which may be annoying but not painful. Investigators will then introduce a tiny, sterile wire needle (an electrode) through the skin at the same location. When the tip of the needle enters the nerve, subjects may again notice involuntary muscle twitches or tingling in the leg. Investigators will then turn the electrical stimulator off and make minor adjustments in the position of the needle until investigators begin to record the nerve signals. The recording needle will remain in position throughout the study.; Subjects will perform a rhythmic handgrip exercise at 30% or 45% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise; Subjects will perform a sustained handgrip exercise at 30% of maximal voluntary contraction for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this handgrip exercise.; Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following sustained handgrip exercise; Subjects will perform a cycling arm exercise with a stationary cycling device. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline and following this exercise.; Subjects will place hand in cold water with ice for 3 minutes. Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure, and sympathetic nerve activity (SNA) at baseline, during and 2 minutes after the test.
Intervention MeSH terms: Amlodipine; Eplerenone
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hypertension; blood pressure; Aldosterone; Eplerenone; Amlodipine; Primary aldosteronism; Exercise pressor reflex; handgrip exercise; passive arm cycling; active arm cycling

Summary:

      Hypertensive patients often show an exaggerated rise in blood pressure during exercise
      through overactivity of the exercise pressor reflex. An increasing body of evidence suggests
      a role for aldosterone in augmenting the exercise pressor reflex in hypertensive humans. We
      hypothesize that this effect of aldosterone is mediated by its direct action on the central
      nervous system and that administration of mineralocorticoid receptor antagonists constitute
      an effective treatment for EPR overactivity in hypertension, independent of reductions in
      resting BP.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Experiments will be performed on 3 groups of nondiabetic human subjects:

          -  1) stage I (140-159/90-99 mmHg) subjects with essential hypertension.

          -  2) stage I hypertensive subjects with primary aldosteronism

          -  3) normotensive controls.

        Exclusion Criteria:

          -  1) Any evidence of cardiopulmonary disease, left ventricular hypertrophy or systolic
             dysfunction by echocardiography.

          -  2) Blood pressure averaging ≥160/100 mmHg

          -  3) Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2

          -  4) Diabetes mellitus or other systemic illness

          -  5) Pregnancy

          -  6) Hypersensitivity to nitroprusside, phenylephrine, amlodipine or eplerenone

          -  7) Any history of substance abuse or current cigarette use

          -  8) Any history of psychiatric illness

          -  9) History of malignancy