Study: NCT01502787

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Nebivolol
Description: The subject will be started on nebivolol (Bystolic) 5-20mg daily, which he or she will continue for a period of 12 weeks. Following the 12-week treatment period, the procedures listed below will be performed. After completion of the study procedures, the medication will be discontinued.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Forearm blood flow
Description: Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following handgrip exercise (described below), and following Angiotensin II infusion (described below).

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Forearm blood flow
Description: Using high-resolution ultrasound, investigators will measure skeletal muscle blood flow in the forearm at rest, following handgrip exercise (described below), and following Angiotensin II infusion (described below).

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Microneurography
Description: 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.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Microneurography
Description: 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.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Rhythmic handgrip exercise
Description: Subjects will perform a rhythmic 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.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Rhythmic handgrip exercise
Description: Subjects will perform a rhythmic 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.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Lower body negative pressure
Description: Lower body negative pressure increases sympathetic nerve activity. Therefore, investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and after rhythmic handgrip exercise plus lower body negative pressure (LBNP) for 2 minutes.

Intervention type: PROCEDURE
Group type: ACTIVE_COMPARATOR
Intervention: Lower body negative pressure
Description: Lower body negative pressure increases sympathetic nerve activity. Therefore, investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and after rhythmic handgrip exercise plus lower body negative pressure (LBNP) for 2 minutes.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Angiotensin II
Description: Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Angiotensin II
Description: Investigators will measure cardiac output (non-invasive impedance plethysmography), blood pressure and sympathetic nerve activity at baseline and during intravenous infusion of Angiotensin II at the dose of 1, 2, and 3 ng/kg/min for 15 minutes at each dose.