Increased intrinsic excitability of muscle vasoconstrictor sympathetic preganglionic neurones in neonatal spontaneously hypertensive rats

Abstract

Young, spontaneously hypertensive (SH) rats show an increased level of sympathetic activity that predates the development of hypertension (Simms et al 2009 J Physiol).We have examined the properties of muscle vasoconstrictor sympathetic preganglionic neurones (MVC‐SPN) in neonatal SH and Wistar rats. Whole‐cell recordings were obtained from SPN (Wistar n=169, SH n=76; aged p9–14) in T3–4 segment of the working heart‐brainstem preparation.SPN of SH rats showed a higher firing frequency (1.7 vs 3.0Hz) and smaller AHP amplitude. When analysed by functional subgroup it was apparent that these difference were secondary to changes in the excitability of MVC‐SPN. These showed significantly higher firing frequencies (2.2 vs 3.5Hz) with increased respiratory modulation. Additionally, the SH MVC‐SPN had shorter, smaller AHPs, lower input resistances and a weaker transient rectification (IA).Voltage clamp analysis of spontaneous excitatory synaptic events in MVC‐SPN showed similar frequencies and amplitudes of EPSCs. There was a modest preponderance of large EPSCs in SH rats (>30pA, <0.3Hz) which alone did not account for the increased spike discharge.In summary, the MVC SPN of neonatal SH rats are intrinsically more excitable. These changes occur prior to, and may play a causal role in, the development of hypertension.