Contributor Si-Cheng Dai
Cardiovascular diseases are the leading cause of death worldwide, stroke is the number three cause of death in Canada, and chronic kidney disease affects one in ten Canadians. All of these maladies share a common risk factor: hypertension, or high blood pressure. Since the 1980s, salt intake has been known to increase blood pressure. More recently, evidence has suggested that part of this increase is controlled by the sympathetic nervous system, which regulates our “fight-or-flight” response.
Kengo Nomura and his colleagues, working at the National Institute for Basic Biology and several other institutions in Japan, wanted to determine the specific sympathetic pathway by which salt intake increases blood pressure. In doing so, they hoped to unearth structures in the brain that could be targeted by therapies to relieve salt-induced hypertension.
Importantly, these researchers already had a lead. They believed that Nax channels kickstarted this sympathetic response. The Nax channel is a well-researched sodium sensor (sodium being a key component of salt). It is found on neuron-supporting cells in the organum vasculosum lamina terminalis (OVLT), a part of the brain that connects to the hypothalamus to control sympathetic nerve activity. By experimenting with genetically modified mice that did not express Nax channels (known as Nax knockout mice), Dr. Nomura and his team were able to deduce many components of the salt-induced sympathetic pathway involved in elevating blood pressure.
One such component is ASIC1a, a sodium channel found on neurons of the OVLT. In ordinary mice exposed to high amounts of salt, blood pressure and the firing of OVLT neurons to the hypothalamus increased; however, upon chemical blockage of ASIC1a, these two variables no longer changed in response. This demonstrated not only that ASIC1a helps increase blood pressure after high salt is detected, but that it likely does so through activation of the sympathetic nervous system. Meanwhile, in Nax knockout mice exposed to high amounts of salt, blood pressure was expectedly unchanged; chemical blockage of ASIC1a yielded no difference. This verified ASIC1a as part of the same salt-induced, blood pressure-increasing sympathetic pathway as the Nax channels.
All in all, these scientists have advanced our understanding of how the sympathetic nervous system increases blood pressure upon salt intake, uncovering key contributors like the Nax channels and ASIC1a. Further research on such contributors may allow scientists to develop therapies to inhibit them, reversing hypertension in people highly sensitive to salt.
Journal Reference:
1. Nomura K, Hiyama TY, Sakuta H, Matsuda T, Lin CH, Kobayashi K, Kobayashi K, Kuwaki T, Takahashi K, Matsui S, Noda M. [Na+] Increases in Body Fluids Sensed by Central Nax Induce Sympathetically Mediated Blood Pressure Elevations via H+-Dependent Activation of ASIC1a. Neuron. 2019 Jan 2;101(1):60–75.e6.