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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Atherosclerosis, Heart Failure, Congestive, Hypertension, Myocardial Infarction

Intervention / Treatment
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* Drug: Angiotensin II type 1 receptor antagonists


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Angiotensin II type 1 receptor antagonists|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angiotensin Receptor Antagonist, Atherosclerosis, Blood Flow, Endothelium, Endothelial Dysfunction