Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells.
Until recently, the signaling events elicited in vascular smooth muscle cells by angiotensin II (Ang II) were considered to be rapid, short-lived, and divided into separate linear pathways, where intracellular targets of the phospholipase C-diacylglycerol-Ca(2+) axis were distinct from those of the tyrosine kinase- and mitogen-activated protein kinase- dependent pathways. However, these major intracellular signaling cascades do not function independently and are actively engaged in cross-talk. Downstream signals from the Ang II-bound receptors converge to elicit complex and multiple responses. The exact adapter proteins or "go-between" molecules that link the multiple intracellular pathways await clarification. Ang II induces a multitude of actions in various tissues, and the signaling events following occupancy and activation of angiotensin receptors are tightly controlled and extremely complex. Alterations of these highly regulated signaling pathways in vascular smooth cells may be pivotal in structural and functional abnormalities that underlie vascular pathological processes in cardiovascular diseases such as hypertension, atherosclerosis, and post-interventional restenosis.
Touyz
R M
RM
Medical Research Council of Canada Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada. touyzr@ircm.qc.ca
Schiffrin
E L
EL
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000209:etiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011945:Receptors, Angiotensin / Q000502:physiology; D015398:Signal Transduction
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases