The secondary endpoint is Plasma Norepinephrine (PNE), a marker of sympathetic activity, measured by both relative and absolute changes from baseline. PNE will be determined from venous (antecubital area) blood samples and quantified via high performance liquid chromatography (HPLC). PNE will be measured following a fasting blood draw collected between the hours of 7:00 and 10:00 am, preceded by 30 minutes supine rest in a quiet, temperature-controlled room.

Carotid-Femoral Pulse Wave Velocity (CFPWV) will be will be measured by both relative and absolute changes from baseline. CFPWV determined via transcutaneous tonometry of the carotid and femoral arteries will be recorded consecutively. The transit time (TT) between the foot and the pressure waves measured at each location will be determined by using the R-wave of the ECG recording taken during the tonometry procedure as a timing reference.

Circulating levels of vasoconstrictor molecules ET-1 and Ang-2 will be measured by both relative and absolute changes from baseline. ET-1 and Ang-2 will be assessed by enzyme-linked immunosorbent assays (ELISA.)

We asses the influence of circulating factors on endothelial NO and ROS by measuring both relative and absolute changes from baseline. We will expose cultured human umbilical vein endothelial cells (HUVECs, American Type Culture Collection) ex vivo, to media conditioned with serum drawn from participants' blood samples to determine if IMST improves endothelial function via changes in circulating factors that increase endothelial cell NO production and/or reduce endothelial ROS production.

Muscle Sympathetic Nerve Activity (MSNA) will be measured by both relative and absolute changes from baseline. MSNA recorded via microelectrode inserted into the common peroneal nerve immediately posterior to the fibular head. Electrode placement will be confirmed via electrical stimulation. Burst frequency (burst/min) and burst incidence (bursts per 100 heart beats) and total activity (mean burst area /min) will be obtained from the integrated MSNA signal.

Casual (resting) measures of diastolic blood pressure will be assessed in accordance with American College of Cardiology/American Heart Association guidelines. Measurements will be taken using an automated oscillometric sphygmomanometer and will be performed in triplicate over the brachial artery of the non-dominant arm after 5 minutes of quiet rest, with 1 minute of recovery between measures. DBP will be defined as the average of the 3 pressures.

We will obtain continuous measures of diastolic blood pressure over a 24-h period with an FDA approved and European Society of Hypertension validated Non-Invasive Ambulatory Blood Pressure monitor. Blood pressure data will be broken into daytime (16 hour) and nighttime (8 hour) segments according to participants' individual sleep-wake cycles. Mean systolic and diastolic blood pressures (mmHg) will be calculated for the daytime and nighttime periods to evaluate circadian systolic and diastolic blood pressure profiles.

A six-minute walk test will be performed in a 30-meter hallway with cones to mark the ends of the track. The subject will be instructed to walk as quickly as they can, without running, for six minutes. They will start at the first cone and walk down the hallway, rounding the second cone, and returning up the hallway toward the first cone. They will continue to walk up and down the hallway, completing as many laps as possible in six minutes. Subjects will be told how much time is remaining every minute of the test, and with 30 seconds and 10 seconds remaining, and encouraged to walk as quickly as possible each time. Distance covered in six minutes will be recorded.

Subjects will complete the 7 cognitive domain assessments from the NIH Toolbox for the Assessment of Neurological and Behavioral Function. These tests include: 1) flanker inhibitory control and attention test; 2) dimensional change card sort test; 3) list sorting working memory test; 4) picture sequence memory test; 5) oral reading recognition test; 6) picture vocabulary test; and 7) pattern comparison processing speed test. All tests will be performed on an iPad with an investigator presenting task instructions and monitoring compliance, as recommended by the American Academy of Neurology.

Maximal inspiratory pressure (PImax) will be assessed by having subjects generate 3 maximal inspiratory efforts against 3 cmH2O resistance measured at the mouth with a POWERbreathe™ KH2 trainer. If there is > 10% difference between efforts, subjects will perform up to 3 more efforts to ensure PImax is achieved. The average of the 3 greatest pressures.

Resting heart rate will be measured simultaneously with blood pressure using the same automated oscillometric sphygmomanometer as is used for blood pressure assessments. As with blood pressure, heart rate will be defined as the average of the three readings.

Severity of obstructive sleep apnea (i.e., AHI) will be assessed with a Nox T3s Home Sleep Apnea Testing diagnostic device, a Type III polygraph with actigraphy. Subjects will be instructed on the use and fitting of the device. They will be instructed to turn on the device immediately prior to going to bed and to turn it off upon waking. Subjects with an AHI < 15 will be excluded from the study. Outcomes include total sleep time, apneas/hour, hypopneas/hour, average O2 saturation (SpO2), minimum SpO2, duration of SpO2 < 90%, and duration of SpO2 < 85%.

Maximal grip strength will be obtained with a Jamar hydraulic grip strength dynamometer. Handle position of the dynamometer will be standardized at position II. The subject will be seated with the shoulder in neutral position and the elbow supported and flexed to 90◦ with the forearm and wrist in neutral position. The subject will squeeze the dynamometer handle as hard as possible for 3 seconds and maximal force will be recorded in kg. The subject will perform three trials with each hand, and 15 seconds rest will be allowed between trials. Peak force of each hand will be used for analysis.