Recent advances in intracellular signalling in hypertension.
OBJECTIVE
Transmission of external signals from the cell surface to the internal cellular environment occurs via tightly controlled complex transduction pathways. Alterations in these highly regulated signalling cascades in vascular smooth cells may play a fundamental role in the structural, mechanical and functional abnormalities that underlie vascular pathological processes in hypertension. The present review focuses on recent developments relating to two novel signalling pathways: angiotensin II signalling through tyrosine kinases; and oxidative stress and redox-dependent signal transduction. These pathways are emerging as critical mediators of hypertensive vascular disease because they influence multiple cellular responses that are involved in structural remodelling, vascular inflammation and altered tone.


RESULTS
A recent advance in the field of angiotensin II signalling was the demonstration that, in addition to its vasoconstrictor properties, angiotensin II has potent mitogenic-like and proinflammatory-like characteristics. These actions are mediated through phosphorylation of both nonreceptor tyrosine kinases and receptor tyrosine kinases. It is also becoming increasingly apparent that many signalling events that underlie abnormal vascular function in hypertension are influenced by changes in intracellular redox status. In particular, increased bioavailability of reactive oxygen species (oxidative stress) stimulates growth-signalling pathways, induces expression of proinflammatory genes, alters contraction-excitation coupling and impairs endothelial function.


CONCLUSIONS
A better understanding of the molecular pathways that regulate vascular smooth muscle cell function will provide further insights into the pathophysiological mechanisms that contribute to vascular changes and end-organ damage associated with high blood pressure, and could permit identification of potential novel therapeutic targets in the prevention and management of hypertension.
Touyz
Rhian M
RM
Canadian Institute of Health Research Multidisciplinary Research Group on Hypertension, Quebec, Canada. touyzr@ircm.qc.ca
D000804:Angiotensin II / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D017136:Ion Transport; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases