Abstract
The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension.
Highlights
The crucial role of the immune system in hypertension is widely recognized
We have found that placental growth factor (PlGF), an angiogenic growth factor belonging to the vascular endothelial growth factor (VEGF) family, links the nervous drive to immune system activation[7]
Our results demonstrate that hypertensive challenges exploit a cholinergic-sympathetic drive, realized through a vagus-splenic nerve connection, to activate the T cells that eventually migrate to target organs and contribute to blood pressure regulation
Summary
We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. We show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking a7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. We show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. Two main questions remain unanswered: (i) which splanchnic nervous compartment is responsible for these effects on immunity and blood pressure regulation and (ii) how is the brain-to-splanchnic compartment connection established at the onset of hypertension
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