gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

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Truncated PDGFalpha abolishes vasoconstriction in spontaneously hypertensive rats

Veränderungen des PDGFalpha Rezeptors verhindern die Vasokonstriktion bei spontanhypertensiven Ratten

Meeting Abstract (Hypertonie 2003)

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  • M. Tepel - Berlin, D
  • presenting/speaker Z. Zhu - Berlin, D
  • S. Zhu - Berlin, D
  • J. Jing - Berlin, D

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP81

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2003/03hoch181.shtml

Published: November 11, 2004

© 2004 Tepel et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

Binding of platelet-derived growth factor (PDGF) to its receptors ( PDGFR-alpha/beta) initiates intracellular signaling pathways leading to proliferation of vascular smooth muscle cells (VSMC) or vasoconstriction.

Design and Methods

To determine whether mutations of truncated PDGFR-alpha functional domaine reduce the activation of the PDGFR¡Valpha in spontaneously hypertensive rats (SHR), we constructed truncated PDGFR-alpha by gene recombination (Ad5CMV-PDGFR-alpha). Immunoblotting was used to assess tyrosine phosphorylation of PDGFR-alpha immunoprecipitated from cultured rat aortic VSMC, which were transfected with either empty vector for control or transfected with PDGFR-alpha encoding adenoviruses. Incorporation of 3H-thymidine and 3H-Leucine was measured, and intracellular free calcium in VSMC was obtained using fura-2 spectrofluorometry. Vascular reactivity of aortic rings was studied using an isometric force transducer.

Results

Truncated PDGFR-ƒÑ (Ad5CMV-PDGFR-alpha) significantly reduced PDGF-mediated 3H-thymidine incorporation into VSMC compared to control values (160¡Ó7Bq/well vs 204¡Ó9 Bq/well, mean¡ÓSEM, each n=8, p<0.05). Truncated PDGFR-alpha significantly reduced PDGF-mediated 3H-Leucine incorporation into VSMC compared to control values (722¡Ó42Bq/well vs 1027¡Ó32 Bq/well, each n=8, p<0.05). The PDGF¡Vinduced increase of intracellular free calcium concentration was significantly lower in VSMC transfected with truncated PDGFR-alpha compared with controls (108¡Ó9 nmol/L vs 218¡Ó7 nmol/L, n=10, p<0.01). On the other hand, insulin-induced proliferation of VSMC was not significantly reduced in VSMC transfected with truncated PDGFR-alpha. Reactivity of aortic rings to angiotensin II stimulation was significantly reduced after incubation with truncated PDGFR-alpha receptor encoding adenoviruses for 4 hours (0.14¡Ó0.03g vs 0.17¡Ó0.03g, n=6, p<0.01).

Conclusion

Truncated PDGFR-alpha reduces vasconstriction and vascular growth in primary hypertension.