Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats

Interruption of the activity of neurons in the commissural portion of the nucleus of the solitary tract (cNTS) decreases blood pressure (BP) in experimental models of hypertension, such as the spontaneously hypertensive (SH) rat. To examine whether PHOX2B expressing cNTS neurons are involved in maintaining the elevated BP, we used replication-deficient viruses with a modified Phox2 binding site promoter to express the inhibitory chemogenetic allatostatin receptor or green fluorescent protein in the cNTS. Following administration of allatostatin, we observed a depressor and bradycardic response in anesthetized SH rats that expressed the allatostatin receptor. Injection of allatostatin did not affect BP or heart rate (HR) in control SH rats expressing green fluorescent protein in the cNTS. Immunohistochemistry showed that the majority of transduced cNTS neurons were PHOX2B-immunoreactive and some also expressed tyrosine hydroxylase. We conclude that in anesthetized SH rat, the Phox2B expressing cNTS neurons maintain elevated BP

Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats

Interruption of the activity of neurons in the commissural portion of the nucleus of the solitary tract (cNTS) decreases blood pressure (BP) in experimental models of hypertension, such as the spontaneously hypertensive (SH) rat. To examine whether PHOX2B expressing cNTS neurons are involved in maintaining the elevated BP, we used replication-deficient viruses with a modified Phox2 binding site promoter to express the inhibitory chemogenetic allatostatin receptor or green fluorescent protein in the cNTS. Following administration of allatostatin, we observed a depressor and bradycardic response in anesthetized SH rats that expressed the allatostatin receptor. Injection of allatostatin did not affect BP or heart rate (HR) in control SH rats expressing green fluorescent protein in the cNTS. Immunohistochemistry showed that the majority of transduced cNTS neurons were PHOX2B-immunoreactive and some also expressed tyrosine hydroxylase. We conclude that in anesthetized SH rat, the Phox2B expressing cNTS neurons maintain elevated BP.Department of Anatomy and Physiology University of MelbourneDepartment of Physiology and Pathology School of Dentistry São Paulo State University UNESP, SPFlorey Institute of Neuroscience and Mental Health University of MelbourneDepartment of Physiology and Pathology School of Dentistry São Paulo State University UNESP, S

Experimental study of the material composition of laparoscopic ports on tumour cell adherence

BACKGROUND: Laparoscopic resection of intra-abdominal malignancies has yet to be widely adopted, partly because of concerns over the possible increase in the rate of port-site metastasis. The aetiology of these is unclear, but the laparoscopic instrumentation used may influence the deposition of tumour cells at the port sites during operation. An in vitro model to examine tumour cell adherence to laparoscopic ports and to port sites was developed to examine this hypothesis. METHODS: A pilot study (study 1) was performed in which six smooth plastic, six ribbed plastic and six metal ports were introduced through the shaved abdominal wall of a cadaveric sheep and suspended in a water-bath containing radiolabelled LIM 1215 human colonic cancer cells for 30 min. Radioactivity on both ports and port sites was measured and the number of cells adherent to each structure was calculated. The study was expanded to include a further 36 smooth plastic ports and 36 metal ports (study 2). RESULTS: In study 1 metal ports were found to have significantly more adherent cells than plastic ports (P = 0.004), as did ribbed ports when compared with smooth ports (P < 0.05). In study 2 increased numbers of cells were again detected on metal ports (P < 0.001) when compared with plastic ports. Significantly greater numbers of cells were also detected on the sites through which metal ports had passed than on sites through which plastic ports had passed (P = 0.03). CONCLUSION: In this model, the use of metal ports as opposed to plastic ports resulted in increased deposition of tumour cells on both ports and port sites