In utero exposure to maternal diabetes impairs vascular expression of prostacyclin receptor in rat offspring.
OBJECTIVE
To evaluate modifications of arterial structure, gene expression, and function in our model of rats exposed to maternal diabetes.


METHODS
Morphometric analyses of elastic vessels structure and determination of thoracic aortic gene expression profile with oligonucleotide chips (Agilent, G4130, 22k) were performed before the onset of established hypertension (3 months).


RESULTS
Arterial parameters of in situ fixed thoracic aorta were not significantly different between control mother offspring and diabetic mother offspring (DMO). The aortic gene expression profile of DMO is characterized by modifications of several members of the arachidonic acid metabolism including a twofold underexpression of prostacyclin receptor, which could contribute to decreased vasodilatation. This was confirmed by ex vivo experiments on isolated aortic rings. Pharmacological studies on conscious rats showed that systolic blood pressure decline in response to a PGI(2) analog was impaired in DMO rats.


CONCLUSIONS
These results suggest an abnormal vascular fetal programming of prostacyclin receptor in rats exposed in utero to maternal hyperglycemia that is associated with impaired vasodilatation and may be involved in the pathophysiology of hypertension in this model.
Duong Van Huyen
Jean-Paul
JP
NSERM U872, Centre de Recherche des Cordeliers, Universite's Pierre et Marie Curie et Paris-Descartes, Paris, France. celine.fassot@inserm.fr
Vessières
Emilie
E
Perret
Claudine
C
Troise
Adrien
A
Prince
Sonia
S
Guihot
Anne-Laure
AL
Barbry
Pascal
P
Henrion
Daniel
D
Bruneval
Patrick
P
Laurent
Stéphane
S
Lelièvre-Pégorier
Martine
M
Fassot
Céline
C
D000818:Animals; D001013:Aorta, Thoracic / Q000196:embryology / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure; D018076:DNA, Complementary / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000503:physiopathology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D044006:Receptors, Epoprostenol / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014664:Vasodilation
D018076:DNA, Complementary; D044006:Receptors, Epoprostenol; D016718:Arachidonic Acid; D012313:RNA