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Home > "R" Clinical Trials Conditions > Role of Endothelin in the Regulation of Vascular Tone in Patients with Essential Hypertension  Role of Endothelin in the Regulation of Vascular Tone in Patients with Essential Hypertension
Role of Endothelin in the Regulation of Vascular Tone in Patients with Essential Hypertension
For Condition: Hypertension
Status: Completed
Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) ,
Synopsis: Endothelin-1 (ET-1) is a powerful vasoconstricting peptide produced predominantly by vascular endothelial cells, that exerts its effect through the interaction with specific receptors, ETA and ETB, on the underlying smooth muscle cells. Previous studies in normal subjects have demonstrated an increase in forearm blood flow after ET-1 antagonism, suggesting a physiologic role of ET-1 in the regulation of basal vascular tone. However, whether ET-1-mediated tone is increased in hypertensive patients is unknown. The main purpose of this study will be to compare the forearm vascular responses to local infusion of ET-1 receptor antagonists between normotensive and hypertensive subjects in order to assess whether ET-1-mediated basal tone is increased in patients with hypertension. In addition, we propose to study the vascular responses to local ET-1 infusion to determine whether vascular smooth muscle sensitivity to this peptide is increased in hypertensive vessels. We will use both an ETA receptor antagonist, BQ-123, and an ETB receptor antagonist, BQ-788, in order to evaluate the relative contribution of the two receptor subtypes to the regulation of vascular tone. All drugs will be infused into the brachial artery and the responses of the forearm vasculature will be measured by means of strain gauge plethysmography. Because of the relative long-lasting effect of most of the substances to be infused, the study will be performed on two separate occasions.
Details: Endothelin-1 (ET-1) is a powerful vasoconstricting peptide produced predominantly by vascular endothelial cells, that exerts its effect through the interaction with specific receptors, ETA and ETB, on the underlying smooth muscle cells. Previous studies in normal subjects have demonstrated an increase in forearm blood flow after ET-1 antagonism, suggesting a physiologic role of ET-1 in the regulation of basal vascular tone. However, whether ET-1-mediated tone is increased in hypertensive patients is unknown. The main purpose of this study will be to compare the forearm vascular responses to local infusion of ET-1 receptor antagonists between normotensive and hypertensive subjects in order to assess whether ET-1-mediated basal tone is increased in patients with hypertension. In addition, we propose to study the vascular responses to local ET-1 infusion to determine whether vascular smooth muscle sensitivity to this peptide is increased in hypertensive vessels. We will use both an ETA receptor antagonist, BQ-123, and an ETB receptor antagonist, BQ-788, in order to evaluate the relative contribution of the two receptor subtypes to the regulation of vascular tone. All drugs will be infused into the brachial artery and the responses of the forearm vasculature will be measured by means of strain gauge plethysmography. Because of the relative long-lasting effect of most of the substances to be infused, the study will be performed on two separate occasions.
Eligibility:
Study Type: Observational, Natural History
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: Between 40-65 years old. Normal Volunteers who are not taking medications. Have no medical problems. Cholesterol below 200 mg/dl. No contraceptives. Hypertensive Patients with blood pressure greater than 145/90 off medications. Serum cholesterol less than 200 mg/dl. No other medical problems. High cholesterol patients with cholesterol level greater than 250 mg/dl. No other medical problems.
Total Enrollment: 60
Location and Contact Information:
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
United States
Additional Information:
Study ID Numbers: 960016; 96-H-0016
Study Start Date: November 28, 1995
Record last reviewed: November 19, 1999
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00001527
Other Hypertension Studies:
1. National Heart, Lung, and Blood Institute Twin Study
2. PET Scan in Patients with Neurocardiologic Disorders
3. Strong Heart Study
4. Urban African-American Community Hypertension Control
5. Suppressed Anger, Blood Pressure and Mortality Follow-up
Related Studies:
Other Hypertension Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Role of Endothelin in the Regulation of Vascular Tone in Patients with Essential Hypertension
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