ABSTRACT

INTRODUCTION Type I (AT 1) angiotensin II receptor ( ubtype AT 1A and AT 18) mediate the important cardiovascular, neuromodulatory, endocrine and growth-promoting actions of the peptide hormone, angiotensin II (Ang II). After activation of the renin-angioten in ystem, AT 1 receptor tran form the extracellular generation of Ang II into multiple intracellular ignaling pathways that predicate cellular Ang ll re pon e . LogicaJiy, any mechani m that modulates the number or function of AT 1 receptor at the cell urface can alter the re pon ivenes of cell and ti ue to Ang ll. Therefore, it i not urpri ing that cell have evolved multiple proce e to regulate receptor activity and den ity, both acutely and gradually, and that u urping the e regulatory proce e can cau e homeostatic and cardiova cular imbalances. For example, when the AT 1A receptor wa overexpre ed in transgenic mice, using an a-myo in heavy chain promoter to direct ex pres ion in cardiac myocytes (Hein el al., J997b) , the newborn mice di played atrial enlargement, myocyte hyperpla ia with an a ociated bradycardia and heart block, and premature death . Thi clearly illu trate the con equence of uncontrolled AT lA ignaling in the heart, and corroborate a vast literature correlating overactivity of the renin-angioten in y tern and cardiova cular dy function. It al o erve to under core the importance of under tanding the mechani ms that regulate AT 1 receptor function.