Editors' ChoiceVasorelaxation

Hydrogen Peroxide and Blood Pressure

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Science's STKE  11 Sep 2007:
Vol. 2007, Issue 403, pp. tw330
DOI: 10.1126/stke.4032007tw330

The guanosine 3′,5′-monophosphate (cGMP)-dependent protein kinase (PKG) functions in the control of blood pressure. Regulation of the enzyme can occur as a consequence of signaling by NO, which stimulates formation of cGMP. The cGMP binds to PKG and activates it, which causes vasorelaxation (reduced tension of smooth muscle in blood vessel walls). Burgoyne et al. (see the Perspective by Hartzell) present evidence for another mechanism of control of the activity or the Iα isoform of PKG. This isoform appears to directly sense the presence of oxidants in the cell. In the presence of H2O2, PKGIα formed disulfide-linked dimers that had increased affinity for kinase substrates and showed increased enzymatic activity. Treatment of heart tissue or aortic rings with H2O2 showed that relaxation was correlated with formation of the enzyme dimer, and relaxation could be produced independently of NO-dependent changes in the concentration of cGMP. The authors propose that physiological agents that alter cellular production of H2O2 may act through such a mechanism to control activity of PKG1α and thus regulate blood pressure.

J. R. Burgoyne, M. Madhani, F. Cuello, R. L. Charles, J. P. Brennan, E. Schröder, D. D. Browning, P. Eaton, Cysteine redox sensor in PKGIα enables oxidant-induced activation. Science 317, 1393-1397 (2007). [Abstract] [Full Text]

H. C. Hartzell, The stress of relaxation. Science 317, 1331-1332 (2007). [Summary] [Full Text]

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