Clinical trial NCT00001629: The Role of Angiotensin Type I Receptor in the Regulation of Human Coronary Vascular Function
Official title: The Role of Angiotensin Type I Receptor in the Regulation of Human Coronary Vascular Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atherosclerosis
Heart Failure, Congestive
Hypertension
Myocardial Infarction
Keywords: Angiotensin AT-1 Receptor
Angiotensin Receptor Antagonist
Atherosclerosis
Blood Flow
Cold Pressor Test
Endothelium
Exercise
Coronary Artery Disease
Heart Failure
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2002-12-10
Enrollment: 49
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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 both endothelial dysfunction and metabolic coronary vasodilation, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on endothelial function are also partly 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: 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 both endothelial dysfunction and metabolic coronary vasodilation, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on endothelial function are also partly 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.

Eligibility criteria: Patient must be over 18 years of age requiring diagnostic cardiac catheterization will participate.

Women on chronic estrogen therapy are eligible for the study.

Patients investigated for chest pain syndrome with normal coronary arteries with and without risk factors for atherosclerosis, patients with coronary artery disease, and patients with heart failure.

No patients with unstable angina; significant left main disease (greater than 50% stenosis); Recent myocardial infarction (less than 1 month); Pregnancy, lactation; Allergy to losartan; Renal failure (creatinine greater than 2.5 mg/dl); Inability to withdraw ACE inhibitors.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Heart, Lung and Blood Institute (NHLBI)
state: Maryland
Study officials:
References:
citation: 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.
citation: Goldberg MR, Tanaka W, Barchowsky A, Bradstreet TE, McCrea J, Lo MW, McWilliams EJ Jr, Bjornsson TD. Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers. Hypertension. 1993 May;21(5):704-13. doi: 10.1161/01.hyp.21.5.704.
citation: Sudhir K, MacGregor JS, Gupta M, Barbant SD, Redberg R, Yock PG, Chatterjee K. Effect of selective angiotensin II receptor antagonism and angiotensin converting enzyme inhibition on the coronary vasculature in vivo. Intravascular two-dimensional and Doppler ultrasound studies. Circulation. 1993 Mar;87(3):931-8. doi: 10.1161/01.cir.87.3.931.