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.

Angiotensin AT-1 Receptor, Angiotensin Receptor Antagonist, Atherosclerosis, Blood Flow, Cold Pressor Test, Endothelium, Exercise, Coronary Artery Disease, Heart Failure

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.

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