Losartan with PTSDRole of Sympathetic Overactivity and Angiotensin II in PTSD and CV

For examining Objective 1 of this study, participants with post-traumatic stress disorder (PTSD) will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine. For the second phase, they will be randomized to either losartan or atenolol.

For examining Objective 1 of this study, healthy controls will be evaluated using microneurography, static handgrip exercise, cold pressor test, combat virtual reality video clip, and baroreflex sensitivity using sodium nitroprusside and phenylephrine.

Participants with PTSD randomized to receive losartan for 8 to 14 weeks.

Participants with PTSD randomized to receive atenolol for 8 to 14 weeks.

Participants with PTSD randomized to receive treatment with tVNS for 8 to 14 weeks.

Participants with PTSD randomized to receive treatment with sham-tVNS for 8 to 14 weeks.

Skin will be stimulated with a pencil-shaped electrode to find a certain nerve. Once the nerve is found, two tiny sterile wire needles (about the size of acupuncture needles) will be put in the skin. One needle is put just under the skin at a short distance away from the nerve, and the other one into the nerve. The needles are attached to a computer recorder to record the nerve activity. It may take up to one hour to get the needles in the right place. After the tiny needle is in the right place, investigators record nerve activity at rest for about 10 minutes. Then, it will be recorded throughout the rest of the visit (up to 4 hours).

Subjects will watch a video clip of combat on a computer screen or wearing video goggles.

Subjects will squeeze a hand dynamometer intermittently.

Subjects' hand will be submerged in cold water (\~0-1°C) up to the wrist for 1 minute.

Subjects will receive sodium nitroprusside 100 µg, which is bolused through an antecubital intravenous catheter.

Subjects will receive phenylephrine 150 µg, which is bolused through an antecubital intravenous catheter 60 seconds after the sodium nitroprusside bolus

Losartan will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.

Atenolol will be administered as 25 mg taken orally, once a day for to 8 to 14 weeks.

Transcutaneous vagal nerve stimulation (tVNS) is administered using the gammaCore (ElectroCore) TENS device. The gammaCore device is a multi-use, hand-held, rechargeable portable device consisting of a rechargeable battery, signal generating and amplifying electronics, and two buttons to power on the device and for operator control of the stimulation intensity (range 0-40). A small amount of conductive gel is applied to the pair of stainless steel round discs on the device are placed vertically on the skin with the gel. The stimulation is increased until there is a strong vibration and slight muscle contraction in the lower face or neck (usual intensity 15-25). Then the dose is delivered for 2 minutes on the left side of the neck, and on the right side of the neck, for a total of 4 minutes of treatment. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day.

A sham device that is identical to the gammaCore device will be provided to participants. Participants will be instructed on the usage of the device and will self-administer up to 4 treatments twice per day.