Effects Of Ammonia On NO/cGMP Passway In Rat Vessel And Heart

In recent years,with the continuous improvement of people′s health awareness,more and more attentions have been paid to the harmfulness of pollution gases to human health.A lot of scientific researches have been done on the harm caused by harmful gases such as formaldehyde and sulfur dioxide.However,as a common pollutant,ammonia is often neglected by people and there is a lack of research on the toxicological effects of ammonia.Through the early isolated rat aortic rings experiment,we found that ammonia can cause the change of vascular tension in vitro.It may be related to NO/cGMP signaling pathway,L type calcium channel and large conductance calcium activated potassium channels.Based on this,in this experiment,Western-blot,PCR and methods for determinations of enzyme activity,were used to investigate the effects of ammonia on the NO/cGMP signaling pathway and two kinds of ion channels of the blood vessels and heart in rats and the main mechanism of the effects.In this study,72 adult male Wistar rats were randomly divided into four groups.The exposed concentrations of ammonia were 27,81 and 243 mg/m3,respectively.The treatment time was 4h for each group every day and lasted for one week.The thoracic aortas and hearts were removed after the last treatment 24 h and quickly frozen them in liquid nitrogen.Then,a series of experiments were carried out by means of protein gel electrophoresis,PCR and enzyme activity assay.The results show that the effects of ammonia on blood vessels and hearts are similar.⑴When the concentration of ammonia reached a certain concentration,it could inhibit the gene expression,protein synthesis and activity of nitric oxide synthase.⑵Ammonia can obviously promote the synthesis of inducible nitric oxide synthase and enhance the activity of inducible nitric oxide synthase.⑶Ammonia could lead to a significant increase in NO and cGMP,and a significant decrease in cAMP content.⑷The gene transcription and protein synthesis of L type calcium channel were significantly inhibited by ammonia.⑸Ammonia reduced the expression of BK_Ca gene in the large conductance calcium activated potassium channel.The above results show that ammonia causes NO/cGMP signaling pathway,L type calcium channel and calcium activated potassium ion channel changes in the blood vessels and heart of rats,which may further affect the physiological function of the cardiovascular system.