Involvement And Mechanism Of Sympathetic System Abnormality In Aortic Dissection

Part? Sympathetic hyperactivity and aortic sympathetic nerve sprouting in patients with thoracic aortic dissectionSubject:To determine the yet unknown relationship between thoracic aortic dissection (TAD) and sympathetic nervous system activity.Methods:Variables such as ECG, blood pressure, respiratory activity, post-ganglionic muscle sympathetic nerve activity (MSN A), Plasma norepinephrine, tyrosine hydroxylase positive nerve fiber density and growth associated protein 43 positive nerve fiber density were detected and Statistical analyzed.Results:TAD Patients showed a significant lower R-R interval variance (1712±331 Vs 2614±499 ms2, p<0.01) and higher blood pressure (systolic 170±43 Vs121±13mmHg, p<0.01; diastolic 120±32 Vs 71±12mmHg, p<0.01), heart rate (84±14 Vs 67±6 bpm), respiratory rate (22±3 Vs 16±2 per min), MSNA (35±4.1 Vs 17±3.3 burst/min, p<0.01), plasma norepinephrine (reflecting elevated sympathetic nervous system (SNS) activity,369±52 Vs 251±41 pg/ml, p<0.01) and higher tyrosine hydroxylase, growth associated protein 43 positive nerve fiber density (reflecting sympathetic sprouting and innervation) than those of the control group (TH+ 44121±1065 Vs 1121±386 um2/mm2, P<0.01; GAP43+46125±1732 Vs 8612±932um2/mm2, P<0.01)Conclusions:In TAD patients, both overall and regional aortic SNS activities are elevated; sympathetic abnormality may be involved in the mechanism of aorticPart? Impact and histological basis of chemical sympathectomy on aortic dissection susceptibility in ratsObject:To investigate the impact and histological basis of chemical sympathectomy on aortic dissection susceptibility in rats.Methods:BAPN (beta Aminopropionitril) mixed food was to induce aortic dissection model in rats. Those model was randomly divided into control group (plus 0.9% sodium chloride injection) and plus guanethidine chemical sympathectomy group (plus guanethidine injection). Animal death and 60 days from the beginning were defined as endpoints. Survival cure were drawn based on the survival time of each rat to make a comparison between two groups. Aorta sample were collected after autopsy. HE and EVG staining were used to investigate the difference of the elastic layer of two groups. qPCR and immunohistochemistry were performed to determine MMP2 (matrix metalloproteinase 2), MMP9 and a-SMA gene and protein expression level.Results:Compared to the control group, the plus guanethidine chemical sympathectomy groupshowed delayed aorta rupture(P<0.05 compared by survival curve), decreased elastic layer destroy and down regulated MMP2 gene (0.5±0.14 folds, p<0.01) and protein expression. MMP9 (0.97±0.19 folds, p>0.05) and a-SMA (0.98±0.12folds, p>0.05) expression were not different between two grous.Conclusions:Our experiment provides evidence that chemical sympathectomy can up-regulate the aorta MMP2 expression and protect the animal from BAPN induced aortic dissection. Our results highlight the importance of sympathetic nerve aorta physiology. Abnormality of sympathetic system may be involved in the mechanism of aortic dissection. Sympathetic innervation may be a new target for treating aortic dissection.Part? Ang? enhances noradrenaline release from sympathetic nerve endings thus contributing to the up-regulation of metalloprotease-2 in aortic dissection patients'aorta wallObject:To test the hypothesis that angiotensin II (Ang II) could enhance noradrenaline (NA) release from sympathetic nerve endings of the aorta thus contributing to the up-regulation of matrix metalloproteinase 2 (MMP-2) during the formation of aortic dissection (AD).Methods:Ang ?, NA, MMP-2, MMP-9 of the aorta sample obtained during operation from aortic dissection patients were detected by High Performance Liquid Chromatography and ELISA and compared with controls. Isotope labelling method was used to test the impact of exogenous Ang II and noradrenaline on the NA release and MMP-2, MMP-9 expression on Sprague Dawley (SD) rat aorta rings in vitro. Two kidneys, one clip, models were replicated for further check of that impact in SD rats in vivo.Results:The concentration of Ang ?, MMP-2?9 was increased and NA concentration was decreased in aorta samples from AD patients. Exogenous Ang II enhanced while exogenous NA restrained NA release from aortic sympathetic endings. The Ang II stimulated NA release and the following MMP-2 up-regulation could be weakened by Losartan and chemical sympathectomy. Beta blocker did not influence NA release but down-regulated MMP-2. Long term in vivo experiments confirmed that Ang II could enhance NA release and up-regulate MMP-2.Conclusions:AD is initiated by MMP-2 overexpression as a result of increased NA release from sympathetic nervous endings in response to Ang II. This indicates an interaction of RAS and SAS during the formation of AD.