Carotid body induced post‐inspiratory neuron channelopathy for neurogenic hypertension (872.9)

Abstract

Post‐inspiratory (post‐I)‐modulation of sympathetic outflows was increased in the pre‐hypertensive spontaneously hypertensive (SH) rats and this excitation can be reduced by carotid body denervation (CBD).In SH and Wistar rats (4‐6 week old), simultaneous recordings of sympathetic and respiratory nerves together with whole cell patch clamp recordings of Bötzinger Complex post‐I neurons from in situ preparations were made. We evaluated whether enhanced post‐I modulation of sympathetic activity is due to changes in the intrinsic ionic properties of post‐I neurons and whether this can be reversed by CBD. In SH rats, the increased post‐I modulation of lumbar sympathetic nerve (n=22) was associated with a greater post‐I discharge in laryngeal motor outflow (n=15). These changes are associated with an increased intrinsic excitability and decreased spike frequency adaptation of post‐I neurons in SH(n=8) relative to Wistar (n=8) rats; this was attributed to a reduced calcium activated potassium conductance in SH rat post‐I neurons. Five days after CBD in SH rats the calcium activated potassium conductance in post‐I neurons was similar to that measured in Wistar rats (n=10). Our data support the novel concept of “respiratory neuron channelopathy” mediated by carotid body over activity in SH rats that may contribute to their excessive sympathetic activity.Grant Funding Source: Supported by British Heart Foundation and FAPESP