Cardiovascular Research Advance Access originally published online on July 2, 2008
Cardiovascular Research 2008 80(2):271-279; doi:10.1093/cvr/cvn185
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Apocynin-induced vasodilation involves Rho kinase inhibition but not NADPH oxidase inhibition
Department of Physiology, University of Greifswald, Greifswalder Street 11c, D17495 Greifswald, Karlsburg, Germany
* Corresponding author. Tel: +49 3834 8619300; fax: +49 3834 8619310. E-mail address: grisko{at}uni-greifswald.de
Aims: The present study was designed to test the hypothesis that NADPH oxidase inhibition with apocynin would lower blood pressure and improve endothelial function in spontaneously hypertensive rats (SHRs). Although apocyin effectively dilated arterial segments in vitro, it failed to lower blood pressure or improve endothelial function. Further experiments were performed in normotensive rats and in NADPH oxidase subunit knock-out mice to test if apocynin-induced vasodilation depends on NADPH oxidase inhibition at all.
Methods and results: SHRs were treated with apocynin orally or i.v. Arterial pressure was recorded directly. Rat and mouse arterial function was investigated in vitro by small vessel wire myography. NADPH oxidase activity was measured in human granulocytes and in rat vascular preparations. Rho kinase activity was determined by Western blot analysis. Apocynin did not reduce arterial pressure acutely in SHR when given at 50, 100, or 150 mg kg–1 day–1 orally over 1-week intervals or when given i.v. Apocynin potently inhibited granulocyte NADPH oxidase but not vascular NADPH-oxidase-dependent oxygen radical formation unless exogenous peroxidase was added to vascular preparations. Apocynin dilated rat intrarenal and coronary arteries independently of pharmacological interventions that reduce vascular superoxide radical abundance and actions. Aortic rings from p47phox–/– mice were more sensitive to apocynin-induced dilation than wild-type aortic rings. Rho kinase inhibition reduced or prevented the inhibitory effect of apocynin on agonist-induced vasoconstriction and apocynin inhibited the phosphorylation of Rho kinase substrates.
Conclusion: Apocynin per se does not inhibit vascular NADPH-oxidase-dependent superoxide formation. Its in vitro vasodilator actions are not due to NADPH oxidase inhibition but may be explained at least in part by inhibition of Rho kinase activity. The discrepancy between apocynin-induced vasodilation in vitro and the failure of apocynin to lower arterial pressure in SHR suggests opposing effects on arterial pressure-regulating systems in vivo. Its use as a pharmacological tool to investigate vascular NADPH oxidase should be discontinued.
KEYWORDS Hypertension; NADPH oxidase; Vascular function; Rats; Inbred strains; Rho kinase
Time for primary review: 39 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. E. Dennis, J. L. Aschner, D. Milatovic, J. W. Schmidt, M. Aschner, M. R. Kaplowitz, Y. Zhang, and C. D. Fike NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets Am J Physiol Lung Cell Mol Physiol, October 1, 2009; 297(4): L596 - L607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Potenza, S. Gagliardi, L. De Benedictis, A. Zigrino, E. Tiravanti, G. Colantuono, A. Federici, L. Lorusso, V. Benagiano, M. J. Quon, et al. Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E685 - E694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. C. Kopp, O. Grisk, M. Z. Cicha, L. A. Smith, A. Steinbach, T. Schluter, N. Mahler, and T. Hokfelt Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R337 - R351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, A. K. Sharma, M. Marshall, I. L. Kron, and V. E. Laubach NADPH Oxidase in Bone Marrow-Derived Cells Mediates Pulmonary Ischemia-Reperfusion Injury Am. J. Respir. Cell Mol. Biol., March 1, 2009; 40(3): 375 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Godbole, X. Lu, X. Guo, and G. S. Kassab NADPH oxidase has a directional response to shear stress Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H152 - H158. [Abstract] [Full Text] [PDF]
|
|