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

<p>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 &#956;mol/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 &#956;M, 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.</p>

Name thesis:degree_name

PhD (Doctor of Philosophy)

Level thesis:degree_level

Dissertation - unrestricted

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.issued

2003

Author dc:creator

• Tompkins, John Daniel

• DOCA
• sympathetic ganglia
• electrophysiology
• substance P
• SHR
• hypertension
• Medical Sciences
• Medicine and Health Sciences

Statement dc:rights

• Copyright by the authors.

Repository record dc:identifier

https://dc.etsu.edu/etd/855

OAI identifier oai:identifier

oai:dc.etsu.edu:etd-2012