Characterization of Sympathetic Ganglion Sensitivity to Substance P in a Genetic and a Non-Genetic Rat Model of Hypertension.

• Main Author: Tompkins, John Daniel
• Format: Others
• Published: Digital Commons @ East Tennessee State University 2003
• Subjects: DOCA; sympathetic ganglia; electrophysiology; substance P; SHR; hypertension; Medical Sciences; Medicine and Health Sciences
• Online Access: https://dc.etsu.edu/etd/855; https://dc.etsu.edu/cgi/viewcontent.cgi?article=2012&context=etd

Intravenous injection of substance P (SP) stimulates sympathetic ganglia to evoke a greater increase in renal sympathetic nerve activity, heart rate (HR) and blood pressure (BP) in hypertensive than normotensive rats due to upregulation of the NK1 receptor. These experiments were designed to determine the cellular basis for the enhanced ganglionic responsiveness to NK1 agonists in spontaneously hypertensive rats (SHR) in comparison to their normotensive counterparts, Wistar-Kyoto rats (WKY). Studies were also conducted to determine whether the increased ganglion responsiveness to SP in SHR is causally related to the increased BP or is a unique characteristic of this model of essential hypertension. Nerve recordings were made from the external carotid branch of the superior cervical ganglion (SCG) in pentobarbital anesthetized rats. Animals were treated with the ganglion blocking agent chlorisondamine (10.5 μmol/kg) and pre- and postganglionic SCG nerves were cut. SP (1.0 to 100 nmol/kg) evoked a greater increase in postganglionic nerve firing from the SCG of SHR vs. WKY. Intracellular microelectrode recordings were made from isolated SCG. Membrane properties were similar between strains. Picospritzer application of the NK1 agonist GR-73632 (100 μM, 1 s) caused slow depolarization and increased neuron excitability. Depolarization amplitude and duration were similar between strains, however, a greater percentage of neurons were depolarized by the NK1 agonist in SHR. To determine if the ganglion sensitivity to SP was correlated with blood pressure WKY were made hypertensive by unilateral nephrectomy and deoxycorticosterone acetate (DOCA)/salt treatment. Tail cuff BP was the same in treated WKY and untreated SHR. Increases in sympathetic nerve activity, HR and BP in response to SP (1.0 to 100 nmol/kg) were the same in treated and untreated WKY rats. In conclusion, SHR are more responsive to ganglion stimulation by NK1 agonists due to a greater number of responsive cells within their SCG rather than an enhanced responsiveness of individual neurons. The increased sympathetic nerve responsiveness to SP is an inherent characteristic and not an adaptive response of sympathetic ganglion neurons to hypertension. This enhanced action of SP at sympathetic ganglia may contribute to the elevated sympathetic outflow observed in this model of hypertension.