The Role of Angiotensin Type I Receptor in the Regulation of Human Peripheral Vascular Function

NCT00001628 | Completed Phase 3

• 2 other identifiers: 97014097-H-0140
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The renin angiotensin system (RAS) plays an important physiological and pathophysiological role in the control of blood pressure and plasma volume. Inhibition of the RAS is useful in the treatment of hypertension, cardiac failure and in some patients with myocardial infarction. Several recent clinical trials with angiotensin converting enzyme inhibitors (ACEI) have shown that they also reduce the incidence of myocardial infarction, but the mechanisms underlying this anti-ischemic effect are poorly understood. ACEI reduce angiotensin II synthesis and prevent bradykinin degradation. Results from ongoing studies in the Cardiology Branch (Protocol 95-H-0099) designed to investigate the link between ACEI and the vascular endothelium indicate that ACEI improve peripheral endothelial function, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on peripheral endothelial function are also due to inhibition of angiotensin II. The recent development of selective angiotensin II type 1 (AT1) receptor antagonists allows us to specifically examine the effects of angiotensin II on vasomotor activity.

Conditions

Atherosclerosis; Heart Failure, Congestive; Hypertension; Myocardial Infarction

Keywords

Angiotensin Receptor Antagonist; Atherosclerosis; Blood Flow; Endothelium; Endothelial Dysfunction

Interventions

Angiotensin II type 1 receptor antagonists DRUG

Eligibility Criteria

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

Patients over 18 years with endothelial dysfunction requiring diagnostic cardiac catheterization. Normal volunteers or patients undergoing catheterization who have normal coronary arteries without risk factors for atherosclerosis will be used as controls. No unstable angina. No significant left main disease (greater than 50% stenosis). No recent myocardial infarction (less than 1 month). No pregnancy, lactation. No allergy to losartan. No renal failure (creatinine greater than 2.5 mg/dl). Ability to withdraw ACE inhibitors.

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)

• Ontyd J, Schrader J. Measurement of adenosine, inosine, and hypoxanthine in human plasma. J Chromatogr. 1984 May 11;307(2):404-9. doi: 10.1016/s0378-4347(00)84113-4. No abstract available.

  PMID: 6736187 BACKGROUND

• Cockcroft JR, Sciberras DG, Goldberg MR, Ritter JM. Comparison of angiotensin-converting enzyme inhibition with angiotensin II receptor antagonism in the human forearm. J Cardiovasc Pharmacol. 1993 Oct;22(4):579-84. doi: 10.1097/00005344-199310000-00011.

  PMID: 7505360 BACKGROUND

• Gottlieb SS, Dickstein K, Fleck E, Kostis J, Levine TB, LeJemtel T, DeKock M. Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure. Circulation. 1993 Oct;88(4 Pt 1):1602-9. doi: 10.1161/01.cir.88.4.1602.

  PMID: 8403307 BACKGROUND

MeSH Terms

Conditions

Atherosclerosis; Heart Failure; Hypertension; Myocardial Infarction

Interventions

Angiotensin II Type 1 Receptor Blockers

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: July 1, 1997
• Study Completion: September 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-06

Locations

US (1)