8 AT 1 receptors from a number of species have been cloned, 9,10 and 2 subtypes, designated AT 1A and AT 1B, have been identified in rat and mouse. Gene targeting studies confirmed these conclusions. 6,7 Studies using these antagonists suggested that most of the classically recognized functions of the RAS are mediated by AT 1 receptors. Ang receptors can be divided into 2 pharmacological classes: type 1 (AT 1) and type 2, based on their differential affinities for various nonpeptide antagonists. 2–5Īt the cellular level, responsiveness to Ang II is conferred by expression of Ang receptors. The importance of the RAS in clinical medicine is highlighted by the impressive efficacy of pharmacological agents that inhibit the synthesis or activity of Ang II. Along with its importance in maintaining normal circulatory homeostasis, abnormal activation of the RAS can contribute to the development of hypertension and target organ damage. This biological system is a multienzymatic cascade in which angiotensinogen, its major substrate, is processed in a 2-step reaction by renin and Ang-converting enzyme (ACE), resulting in the sequential generation of Ang I and Ang II.
Highly conserved through phylogeny, the RAS is an essential regulator of blood pressure and fluid balance. Our own studies of the physiology of blood pressure regulation have focused on the renin-angiotensin (Ang) system (RAS) using genetically modified mouse models. The Renin-Angiotensin System and Blood Pressure Control Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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