α2-Adrenoceptors Enhance Angiotensin II–Induced Renal Vasoconstriction: Role for NADPH Oxidase and RhoA

摘要: α 2 -Adrenoceptors potentiate renal vascular responses to angiotensin II via coincident signaling at phospholipase C. This leads increased activation of the C/protein kinase C/c-src pathway. Studies suggest that c-src activates reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase/superoxide system, and reactive oxygen species stimulate RhoA/Rho Therefore, we hypothesized NADPH are downstream components signal transduction pathway mediate interaction between -adrenoceptors on resistance. In rat kidneys, both in vivo vitro, intrarenal infusions resistance, UK14,304 (α -adrenoceptor agonist) enhanced this response. Intrarenal Tempol (superoxide dismutase mimetic) or Y27632 (Rho inhibitor) abolished vitro. The was also blocked by inhibitors oxidase (in using chronic gp91ds-tat administration vitro with diphenyleneiodonium). cultured preglomerular smooth muscle cells, II–induced intracellular superoxide (2-hydroxyethidium production) potentiated RhoA (Western blot activated bound binding domain rhotekin). generation C (U73312), protein (GF109203X), (PP1), (diphenyleneiodonium), (Tempol). We conclude involved resistance mediating events