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

Truncated PDGFalpha abolishes vasoconstriction in spontaneously hypertensive rats

Veršnderungen 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. DŁsseldorf, KŲln: 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-ƒ— (Ad5CMV-PDGFR-alpha) significantly reduced PDGF-mediated 3H-thymidine incorporation into VSMC compared to control values (160°”7Bq/well vs 204°”9 Bq/well, mean°”SEM, each n=8, p<0.05). Truncated PDGFR-alpha significantly reduced PDGF-mediated 3H-Leucine incorporation into VSMC compared to control values (722°”42Bq/well vs 1027°”32 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°”9 nmol/L vs 218°”7 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°”0.03g vs 0.17°”0.03g, n=6, p<0.01).

Conclusion

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