Key result
Combined inhibition of the sympathetic nervous system and angiotensin II AT1 receptors significantly decreased MMP-2 mRNA expression by 31% (p<0.01) in juvenile rat aorta compared to control.
Effect estimate: 31% decrease
p-value: p=<0.01
Combined inhibition of the sympathetic nervous system and angiotensin II is more efficient than single inhibition in reducing MMP-2 expression in rat vessels.
Hypothesis-generating for dual sympathetic-AT1 inhibition in juvenile vessels; leaves open translation to human vascular disease.
The aim of our present study is to investigate the interaction between angiotensin II (ANG II) and sympathetic nervous system (SNS) on matrix metalloproteinase MMP-2 and MMP-9 expression and activity in juvenile rat aorta under normal conditions. Sympathectomy with guanethidine and blockade of the ANG II receptors (AT1R) by losartan were performed alone or in combination on new-born rats. mRNA, protein expression and activity of MMP-2 and MMP-9 were examined by Q-RT-PCR, immunoblotting and zymography, respectively. MMP-2 mRNA and protein amount were decreased after sympathectomy or AT1R blockade and an additive effect was observed after combined treatment. However, MMP-9 expression was reduced to the same level in the three treated groups. There were some detectable gelatinolytic activity of the MMPs in both control and treated rats. We concluded that ANG II stimulates directly and indirectly (via sympathostimulator pathway) the MMP-2 expression but seems unable to affect MMP-9 expression through direct pathway. Combined inhibition of SNS and ANG II were more efficient than a single inhibition in reducing MMP amounts in rat vessels.
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Dab et al. (2011) studied Normal conditions (normotensive) (n=40). Sympathectomy (guanethidine) and AT1R blockade (losartan) vs. Sham (saline injections) was evaluated on MMP-2 mRNA expression (31% decrease, p=<0.01). Combined inhibition of the sympathetic nervous system and angiotensin II AT1 receptors significantly decreased MMP-2 mRNA expression by 31% (p<0.01) in juvenile rat aorta compared to control.
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