Role of Endothelin in the Regulation of Vascular Tone in Patients With Essential Hypertension

NCT00001527 | Completed

• 2 other identifiers: 96001696-H-0016
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension

Keywords

BQ-123; BQ-788; Endothelin; Endothelium; Plethysmography; Essential Hypertension

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411-5. doi: 10.1038/332411a0.

  PMID: 2451132 BACKGROUND

• Rubanyi GM, Polokoff MA. Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev. 1994 Sep;46(3):325-415. No abstract available.

  PMID: 7831383 BACKGROUND

• Sakurai T, Yanagisawa M, Takuwa Y, Miyazaki H, Kimura S, Goto K, Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20-27;348(6303):732-5. doi: 10.1038/348732a0.

  PMID: 2175397 BACKGROUND

MeSH Terms

Conditions

Hypertension; Essential Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: November 1, 1995
• Study Completion: September 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-11

Locations

US (1)