부산대학교 도서관

Introduction:Autonomic nervous system (ANS) and vagal tone regulation have a fundamental role in hypertension. Our group demonstrated that the ANS modulates the immune response involved in regulation of blood pressure (BP) in response to hypertensive stimuli as Angiotensin-II (AngII) or deoxycorticosterone acetate salt (DOCA), through a vagal efference modulating the splenic nerve.Methods and Results:In this work we set up a microneurographic method of peripheral nerves modulating the spleen: the splenic sympathetic nerve (splenic sympathetic nerve activity - SSNA) and the pre-gaglionic celiac vagus nerve (celiac vagus nerve activity - CVNA). Mice infused with AngII by subcutaneous osmotic pump and mice stimulated with DOCA-salt pellet (and matched controls) underwent surgical isolation of the splenic nerve or the celiac vagus nerve to record their activity. Both hypertensive stimuli resulted in an increase of SSNA and CVNA. At cellular level, the increase in vagal-splenic activity determined the recruitment of the co-stimulation process of T lymphocytes, necessary to raise BP. To determine how the nervous vagal-splenic coupling is established we exploited two different approaches. 1) Cut the celiac vagus nerve during SSNA in mice subjected to hypertensive stimuli. The results show that we obtain a significant reduction of SSNA and a subsequent inhibition of co-stimulation of T lymphocyte and their egression from the spleen to infiltrate target organs of hypertension. 2) Mimic the electric effect of hypertensive stimuli on the vagus nerve, in mice not subjected to AngII nor DOCA. By electrical stimulation of celiac vagus nerve we recorded a paired increase of SSNA, co-stimulation of lymphocyte T and their egression from the spleen.Conclusions:We demonstrated that different hypertensive stimuli activate a stimulation pattern of the vagus nerve which recruits adaptive immunity through the splenic sympathetic activity.