Losartan – Hypertensive

Mechanisms of Vasoconstriction in Postmenopausal Women

 

Purpose:

An early indicator for cardiovascular disease is decreased blood vessel function and women with high blood pressure have an increased risk.  The purpose of this study is to understand what causes blood vessels to constrict or get smaller in women with high blood pressure.

The inner lining of the blood vessel (called the endothelium), release substances to help control blood vessel function. One of these substances is endothelin-1 (ET-1). Certain hormones that our bodies produce can influence the release of ET-1 such as the hormone Angiotensin II (ANG II), which is a common therapeutic target for high blood pressure.

The aim of the study is to determine if blocking both ET-1 and ANG II are more effective in reducing constriction compared to a single therapy or control conditions. To accomplish this aim, we will measure blood flow in the very small blood vessels in your skin on your forearm while blocking the ET-1 receptors. To do this we will use a technique called microdialysis.

 

Inclusion:

  • You are a woman between the ages of 50-70, you are postmenopausal, and you have high blood pressure.

 

 

 

Exclusion:

  • If you have a history of heart disease, stroke, cancer, diabetes, kidney or liver disease, blood clots
  • If you have a latex allergy
  • If you use tobacco products including cigarettes and chewing tobacco
  • If you have a BMI (body mass index) greater than 35
  • If you use hormone replacement therapy or are pregnant
  • If you are currently taking medication for high blood pressure
  • If your resting blood pressure is greater than 180/100 mmHg

*Note you must meet all the criteria to be included in this study*

Your Participation:

Full participation in this study will require 5 visits. Each visit will last between one and five hours. The first visit is at the Nurse Managed Primary Care Center. The second, third, and fourth visits will take place at the Women’s Cardiovascular Research Laboratory. The fifth visit will take place at the Nurse Managed Primary Care Center. The Nurse Managed Primary Care Center and the Physiology Core Lab are located at 540 S. College Avenue (STAR Health Sciences Complex).

Your participation in this research study is entirely voluntary and you have the right to stop at any time.

 

Study Design:

Visit 1 will consist of a participant screening in the morning. You will be asked to not eat food, alcohol, and caffeine for 12 hours and not to exercise for 24 hours. You will also be given a 24-hour blood pressure monitor to wear following the visit. 

Visit 2 will occur within two weeks of Visit 1. You will be asked not to drink alcohol and caffeine for 12 hours, food for at least 4 hours, and refrain from exercise for 24 hours prior to this visit. You will be asked to bring or wear a short sleeve shirt and shorts. Within 48-72 hours before Visit 2, you will come to the lab to pick up a 24-hour blood pressure monitor and review instructions on how to wear the monitor. You will wear the monitor during the 24 hours before Visit 2. During Visit 2 a catheter will be used to collect blood samples and endothelial cells. An ultrasound will be used to take pictures of the blood vessel in your upper arm (brachial artery). A microdialysis procedure will also take place; more details will be discussed during the consent process. At the end of Visit 2 you will be given the study medication, Losartan, which is a drug that blocks the receptor for Angiotensin II. You will be given 7 days of the medication and instructed to take 1 pill each day at night time (before bed). You should avoid alcohol while using Losartan and not take any potassium supplements or salt substitutes, or NSAIDS (advil, ibuprofen).

Visit 3 will occur on day 7 of taking Losartan. You will be asked to report to the laboratory in the morning after an overnight fast for a blood draw. The blood draw will be used to assess your blood electrolytes and markers of kidney function. The study physician will review the results to determine if you can continue the study medication.

Visit 4 will occur 1 week after Visit 3 or 2 weeks after starting Losartan. You will be asked not to drink alcohol or caffeine for 12 hours, food for at least 4 hours, and refrain from exercise for 24 hours prior to this visit. This visit will be identical to Visit 2.

Visit 5 will consist of an exercise test, most typically on a motorized treadmill, where we will measure your VO2 max, or the maximum rate of your oxygen consumption during exercise. The incline and the speed of the treadmill will increase throughout the protocol. The test will last 8-10 minutes. We may stop the test at any times because of signs of fatigue, discomfort, or changes in your heart rate, ECG (electrocardiogram), or blood pressure, or symptoms you may experience.

 

Compensation:

You will receive full compensation based on partial or full completion of the study. Compensation amount will be discussed during the consent process.