New clinical trials of angiotensin blockade in cardiovascular disease: foreword.

The symposium “New Clinical Trials of Angiotensin Blockade in Cardiovascular Disease” was held on May 19, 1999 at the Marriott Marquis Hotel in New York, NY. It was sponsored by Novartis Pharmaceuticals and chaired by Stevo Julius, Professor of Medicine and Physiology, University of Michigan Medical Center, Ann Arbor, MI and consisted of five 25-minute long lectures. Stevo Julius pointed out that the new family of antihypertensive drugs, angiotensin receptor blockers (ARBs), are remarkably free of side effects and represent a major step forward in the treatment of hypertension. Activation of the renin-angiotensin system contributes to vascular and cardiac hypertrophy and other pathology associated with hypertension. ARBs not only lower arterial pressure but also prevent this pathology. The specific effects of ARBs on cardiovascular pathology must be recognized. The ongoing VALUE trial involving over 14,000 patients in 31 countries is designed to compare valsartan and amlodipine in the treatment of high-risk patients with hypertension and their ability to protect vital organs. Helmy M. Siragy (University of VA, Charlottesville, VA) discussed the role of AT2 receptors in cardiovascular disease; AT2 receptors share only ca 30% homology with AT1 receptors. Angiotensin II has similar affinity for both receptor types. AT2 receptors mediate the effects of angiotensin II on cell differentiation and development. Their activation has an effect often opposite to that produced by activation of AT1 receptors, e.g. inhibition of growth and dephosphorylation. Stimulation of AT2 receptors increases cGMP, NO, and bradykinin release. AT2 knockout mice have higher sensitivity to the pressor effects of angiotensin II. The expression of AT2 receptors decreases with age but increases