Regulation of aortic extracellular matrix synthesis via noradrenergic system and angiotensin II in juvenile rats

Abstract

Context: Extracellular matrix (ECM) synthesis regulation by sympathetic nervous system (SNS) or angiotensin II (ANG II) was widely reported, but interaction between the two systems on ECM synthesis needs further investigation.

Objective: We tested implication of SNS and ANG II on ECM synthesis in juvenile rat aorta.

Materials and methods: Sympathectomy with guanethidine (50 mg/kg, subcutaneous) and blockade of the ANG II AT1 receptors (AT1R) blocker with losartan (20 mg/kg/day in drinking water) were performed alone or in combination in rats. mRNA and protein synthesis of collagen and elastin were examined by Q-RT-PCR and immunoblotting.

Results: Collagen type I and III mRNA were increased respectively by 62 and 43% after sympathectomy and decreased respectively by 31 and 60% after AT1R blockade. Combined treatment increased collagen type III by 36% but not collagen type I. The same tendency of collagen expression was observed at mRNA and protein levels after the three treatments. mRNA and protein level of elastin was decreased respectively by 63 and 39% and increased by 158 and 15% after losartan treatment. Combined treatment abrogates changes induced by single treatments.

Discussion and conclusion: The two systems act as antagonists on ECM expression in the aorta and combined inhibition of the two systems prevents imbalance of mRNA and protein level of collagen I and elastin induced by single treatment. Combined inhibition of the two systems prevents deposit or excessive reduction of ECM and can more prevent cardiovascular disorders.

Keywords::

• Sympathectomy
• angiotensin II AT1-receptor antagonist
• collagen type I and III
• elastin

Acknowledgements

We wish to thank the association “Autour de Williams” for their participation in the financing of reagents used in our experiences. Houcine Dab received a grant from the Ministry of higher education, scientific research and technology (Tunisia) to work on this study in the EA4173, INSERM ERI-22, Faculté Rockefeller, Université Claude Bernard, Lyon 1, France.

Declaration of interest

The authors report no conflicts of interest.