Sympathetic neurotransmission in primary hypertension
Description
Extracellular compound action potential recordings revealed that transmission of physiological rates (1-5 Hz) of preganglionic nerve impulse activity through superior cervical ganglia (SCG) is enhanced in spontaneously hypertensive rats (SHR), the animal model of genetic hypertension used in these studies. Further studies indicated that these same ganglia have a diminished ability to transmit high frequencies ($>$70 Hz) of nerve activity Intracellular EPSP and EPSC recordings from single SCG neurons suggest that the enhanced impulse transmission observed in these ganglia results from an increase in transmitter release by the preganglionic nerve terminals innervating postganglionic SCG neurons. This increased transmitter release results in an elevated EPSP amplitude thereby increasing the efficacy of impulse transmission in SHR sympathetic ganglia. The increased transmitter release also depletes a similarly sized immediately releasable transmitter store to a greater extent in the hypertensive rats when compared to normotensive controls. The enhanced transmitter depletion diminishes the amount of short-term facilitation and enhances synaptic depression, limiting the ability of SHR preganglionic neurons to increase transmitter release during repetitive stimuli. These difference are hypothesized to play a role in the previously mentioned relative inability of SHR ganglia to transmit high frequency nerve impulse activity Whole-cell voltage-clamp recordings from acutely isolated SCG neurons revealed that postsynaptic membrane sensitivity to ACh, and the time course of ACh action are the same in SHR and normotensive controls, suggesting that postganglionic alterations do not play a role in the altered impulse transmission observed in SHR sympathetic ganglia The enhanced ability of SHR sympathetic ganglia to transmit physiological rates of preganglionic nerve activity would result in a greater amplification of preganglionic nerve activity in SHR ganglia, when compared to normotensive controls. This amplification of sympathetic nerve activity would directly contribute to the maintenance of hypertension in this animal model, and may be representative of cellular alteration(s) that are responsible for the enhanced sympathetic nerve activity observed in the SHR. Therefore, these studies further implicate an exaggerated sympathetic nerve activity in the pathogenesis of hypertension in the SHR model and reveal that an alteration of synaptic transmission could underlie the increased nerve activity