NDLI: Down-regulation of vasoactive intestinal peptide and altered expression of its receptors in rat diabetic cardiomyopathy

Content Provider	Springer Nature Link
Author	Dvoráková, Magdalena Chottová Pfeil, Uwe Kuncová, Jitka Švíglerová, Jitka Galvis, Giovanni Krasteva, Gabriela König, Peter Grau, Veronika Slavíková, Jana Kummer, Wolfgang
Copyright Year	2005
Abstract	Vasoactive intestinal peptide (VIP) is a vasorelaxant peptide that addresses two receptor subtypes, VPAC1 and VPAC2. It stimulates insulin secretion and mediates anti-inflammatory effects and has been proposed for treatment of type 2 and autoimmune diabetes. In the heart, VIP is produced and released primarily by intrinsic neurons and improves cardiac perfusion and function. Here, we investigated the involvement of this system in the events underlying development of experimentally induced diabetic cardiomyopathy. Rats received a single streptozotocin injection, and cardiac VIP content [radioimmune assay (RIA)], expression of the VIP precursors VPAC1 and VPAC2 [real-time reverse transcription-polymerase chain reaction (RT-PCR)], and VPAC1 and VPAC2 tissue distribution (immunohistochemistry) were assessed 4, 8, and 16 weeks thereafter and compared with corresponding vehicle-treated controls. Cardiac neuropathy manifests progressively during the first 4 months of diabetes at the preproVIP mRNA and VIP peptide level and is accompanied by initial down-regulation of VPAC2 at one prime target of VIP-containing axons, i.e., smooth muscle cells of coronary arterioles. VPAC1 is expressed by macrophages. After initial changes that are specific for atria and ventricles, respectively, VPAC1 and VPAC2 expression return to control levels at 16 weeks despite ongoing loss of VIP. Given the cardioprotective role of the VIP signaling system, the persistence of receptors has therapeutic implications since it is the prerequisite for trials with VPAC2 agonists.
Starting Page	383
Ending Page	393
Page Count	11
File Format	PDF
ISSN	0302766X
Journal	Cell and Tissue Research
Volume Number	323
Issue Number	3
e-ISSN	14320878
Language	English
Publisher	Springer-Verlag
Publisher Date	2005-12-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Autonomic neuropathy Cardiac ganglia Cardiac innervation Diabetes Heart Rat (Wistar) Molecular Medicine Proteomics Human Genetics
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Pathology and Forensic Medicine

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