Differential control of collagen synthesis by the sympathetic and renin-angiotensin systems in the rat left ventricle.
In the present study, we tested the hypothesis of the indirect (via the sympathetic nervous system (SNS)) and direct (via AT1 receptors) contributions of Angiotensin II (Ang II) on the synthesis of collagen types I and III in the left ventricle (LV) in vivo. Sympathectomy and blockade of the Ang II receptor AT1 were performed alone or in combination in normotensive rats. The mRNA and protein synthesis of collagen types I and III were examined by Q-RT-PCR and immunoblotting in the LV. Collagen types I and III mRNA were decreased respectively by 53% and 22% after sympathectomy and only collagen type I mRNA was increased by 52% after AT1 receptor blockade. mRNA was not changed for collagen type I but was decreased by 25% for collagen type III after double treatment. Only collagen protein type III was decreased after sympathectomy by 12%, but collagen proteins were increased respectively for types I and III by 145% and 52% after AT1 receptor blockade and by 45% and 60% after double treatment. Deducted interpretations from our experimental approach suggest that Ang II stimulates indirectly (via SNS) and inhibits directly (via AT1 receptors) the collagen type I at transcriptional and protein levels. For collagen type III, it stimulates indirectly the transcription and inhibited directly the protein level. Therefore, the Ang II regulates collagen synthesis differently through indirect and direct pathways.
Dab
Houcine
H
Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, Tunisia. houcine.dab@fsb.rnu.tn
Hachani
Rafik
R
Hodroj
Wassim
W
Sakly
Mohsen
M
Bricca
Giampiero
G
Kacem
Kamel
K
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D024042:Collagen Type I / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D024042:Collagen Type I; D024061:Collagen Type III; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D003094:Collagen