QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.050013v1 306/1/8    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seegers, H. C. Articles by Walsh, D. A. Search for Related Content PubMed PubMed Citation Articles by Seegers, H. C. Articles by Walsh, D. A.

CARDIOVASCULAR

Enhancement of Angiogenesis by Endogenous Substance P Release and Neurokinin-1 Receptors During Neurogenic Inflammation

Academic Rheumatology, University of Nottingham Clinical Sciences Building, City Hospital, Nottingham, UK (H.C.S., V.C.H., D.A.W.); and Bone and Joint Research Unit, St. Bartholomew's and the Royal London School of Medicine, London, UK (V.C.H., B.L.K., S.C.C.)

Early angiogenesis is a key step in the transition from acute to persistent inflammation. The nervous system has long been known to play a role in inflammation, in part through the release of substance P from peripheral nerve terminals (neurogenic inflammation). Application of substance P can stimulate vessel growth in a variety of angiogenesis assays, although it was previously not known whether endogenous substance P released from sensory nerves could modulate angiogenesis. We hypothesized that endogenous substance P can initiate angiogenesis during acute neurogenic inflammation. Here we show that 10 nmol of substance P can stimulate angiogenesis within the rat knee synovium, as shown by increased endothelial cell proliferation index [PCNA index, 19% (95% confidence interval (CI), 17 to 20%)] compared with saline injected knees [6% (95% CI, 4% to 8%), p < 0.05]. Moreover, this was prevented by coadministration of an antagonist of the neurokinin-1 (NK₁) subtype of neurokinin receptor SR140333 (nolpitantium), 1 µmol [8% (95% CI, 5% to 11%)]. Capsaicin 0.5%, which stimulates release of endogenous substance P from sensory nerves, was also found to enhance synovial angiogenesis, [PCNA index 17% (95% CI, 14% to 19%)] compared with saline injected control knees [2% (95% CI, 1% to 3%), p < 0.05], and this also was inhibited by 1 µmol of SR140333 [11% (95% CI, 8 to 16%)]. Inhibition of capsaicin-enhanced angiogenesis was incomplete, and this may indicate a contribution of other neuropeptides, in addition to substance P-NK₁ receptor interactions, in capsaicin-enhanced angiogenesis. NK₁ receptor antagonists could have therapeutic potential in conditions where neurogenic angiogenesis contributes to disease.

Address correspondence to: David A. Walsh, Academic Rheumatology, University of Nottingham Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK. E-mail: david.walsh{at}nottingham.ac.uk

This article has been cited by other articles:

				S. BRENER, M. A. GONZALEZ-MOLES, D. TOSTES, F. ESTEBAN, J. A. GIL-MONTOYA, I. RUIZ-AVILA, M. BRAVO, and M. MUNOZ A Role for the Substance P/NK-1 Receptor Complex in Cell Proliferation in Oral Squamous Cell Carcinoma Anticancer Res, June 1, 2009; 29(6): 2323 - 2329. [Abstract] [Full Text] [PDF]

				H.-W. Koon, D. Zhao, H. Xu, C. Bowe, A. Moss, M. P. Moyer, and C. Pothoulakis Substance P-Mediated Expression of the Pro-Angiogenic Factor CCN1 Modulates the Course of Colitis Am. J. Pathol., August 1, 2008; 173(2): 400 - 410. [Abstract] [Full Text] [PDF]

				J. Chui, N. Di Girolamo, M. T. Coroneo, and D. Wakefield The Role of Substance P in the Pathogenesis of Pterygia Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4482 - 4489. [Abstract] [Full Text] [PDF]

				D. Ribatti, M. T. Conconi, and G. G. Nussdorfer Nonclassic Endogenous Novel Regulators of Angiogenesis Pharmacol. Rev., June 1, 2007; 59(2): 185 - 205. [Abstract] [Full Text] [PDF]

				S. Pal, J. Wu, J. K. Murray, S. H. Gellman, M. A. Wozniak, P. J. Keely, M. E. Boyer, T. M. Gomez, S. M. Hasso, J. F. Fallon, et al. An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis J. Cell Biol., September 25, 2006; 174(7): 1047 - 1058. [Abstract] [Full Text] [PDF]

				N. Marquez, L. De Petrocellis, F. J. Caballero, A. Macho, A. Schiano-Moriello, A. Minassi, G. Appendino, E. Munoz, and V. Di Marzo Iodinated N-Acylvanillamines: Potential "Multiple-Target" Anti-Inflammatory Agents Acting via the Inhibition of T-Cell Activation and Antagonism at Vanilloid TRPV1 Channels Mol. Pharmacol., April 1, 2006; 69(4): 1373 - 1382. [Abstract] [Full Text] [PDF]

				C. S. Bonnet and D. A. Walsh Osteoarthritis, angiogenesis and inflammation Rheumatology, January 1, 2005; 44(1): 7 - 16. [Abstract] [Full Text] [PDF]

				A Scott, K M Khan, C R Roberts, J L Cook, and V Duronio What do we mean by the term "inflammation"? A contemporary basic science update for sports medicine Br. J. Sports Med., June 1, 2004; 38(3): 372 - 380. [Abstract] [Full Text] [PDF]

				J.-K. Min, K.-Y. Han, E.-C. Kim, Y.-M. Kim, S.-W. Lee, O.-H. Kim, K.-W. Kim, Y. S. Gho, and Y.-G. Kwon Capsaicin Inhibits in Vitro and in Vivo Angiogenesis Cancer Res., January 15, 2004; 64(2): 644 - 651. [Abstract] [Full Text] [PDF]