(Hypertension. 1997;29:366.)
© 1997 American Heart Association, Inc.
State-of-the-Art-Lecture |
Angiotensin II Signaling in Vascular Smooth Muscle
New Concepts
From the Emory University School of Medicine, Division of Cardiology, Atlanta, Ga.
Correspondence to Kathy K. Griendling, PhD, Emory University, Division of Cardiology, 319 WMB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
Angiotensin II is a multifunctional hormone that affects both contraction and growth of vascular smooth muscle cells through a complex series of intracellular signaling events initiated by the interaction of angiotensin II with the AT1 receptor. The cellular response to angiotensin II is multiphasic, involving stimulation within seconds of phospholipase C and Ca2+ mobilization; activation within minutes of phospholipase D, A2, protein kinase C, and MAP kinase; and stimulation after a period of hours of gene transcription and NADH/NADPH oxidase activity. Angiotensin II also activates numerous intracellular tyrosine kinases. In this respect, it shares some aspects of signaling with growth factor and cytokine receptors, including activation of phospholipase C-
, src, and ras; association of shc with grb2; and stimulation of the Jak/STAT pathway. The cellular events responsible for this unique series of events may involve receptor movement and the creation of a signaling domain. Elucidation of these pathways is important to our understanding of AT1 receptor function as a final effector of the renin-angiotensin system.
Key Words: angiotensin II • vascular smooth muscle • receptor sequestration • phospholipase • tyrosine • phosphorylation • oxidant stress
Abbreviations: Ang II = angiotensin II • AT1 = angiotensin type 1 receptor • GRK(s) = G protein-coupled receptor kinase(s) • MAP = mitogen-activated protein • PLA2, PLC, PLD = phospholipases A2, C, D • VSMC(s) = vascular smooth muscle cell(s)
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