High-glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes

Abstract

glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes. Am J Physiol Heart Circ Physiol 293: H939–H948, 2007. First published May 4, 2007; doi:10.1152/ajpheart.00391.2007.—The prevailing paradigm is that cardiac ANG II is synthesized in the extracellular space from com-ponents of the circulating and/or local renin-angiotensin system. The recent discovery of intracrine effects of ANG II led us to determine whether ANG II is synthesized intracellularly in neonatal rat ventric-ular myocytes (NRVM). NRVM, incubated in serum-free medium, were exposed to isoproterenol or high glucose in the absence or presence of candesartan, which was used to prevent angiotensin type 1 (AT1) receptor-mediated internalization of ANG II. ANG II was measured in cell lysates and the culture medium, which represented intra- and extracellularly synthesized ANG II, respectively. Isoproter-enol increased ANG II concentration in cell lysates and medium o