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