Alterations of synaptic transmission in sympathetic ganglia of spontaneously hypertensive rats

Abstract

An enhanced sympathetic nerve activity (SNA) has been implicated in the development and maintenance of the hypertension observed in experimental animal models such as the spontaneously hypertensive rat (SHR). Recent evidence suggests that an alteration of sympathetic synaptic transmission could also play a significant role in the elevation of SNA observed in the SHR (J. C. Magee and G. G. Schofield. Hypertension Dallas 20: 367-373, 1992). To test this hypothesis, we used intracellular recordings from superior cervical ganglion (SCG) neurons to compare properties of synaptic transmission between SHRs and two normotensive controls [Wistar-Kyoto (WKY) and Wistar rats]. Supramaximal preganglionic stimulation elicited larger amplitude fast excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) in SHR sympathetic neurons compared with the normotensive controls. Analysis of variance of both compound and unitary EPSC amplitudes suggests that an increase in transmitter release is responsible for the elevated EPSP amplitude in these neurons. Also, a diminished short-term facilitation and an elevated synaptic depression limit the ability of SHR preganglionic neurons to increase transmitter release during short trains of repetitive stimuli. It is hypothesized that an enhanced transmitter depletion results in the altered synaptic plasticity of SHR sympathetic ganglion neurons. Intracellular recordings in low-Ca2+, high-Mg2+ external solutions support this idea. Therefore, synaptic transmission between the preganglionic and postganglionic neurons of SCGs from hypertensive rats was found to be altered in a manner that would tend to enhance sympathetic nervous activity, further implicating an exaggerated SNA in the pathogenesis of hypertension in the SHR model.

Angiotensin II regulates neuronal excitability via phosphatidylinositol 4,5‐bisphosphate‐dependent modulation of Kv7 (M‐type) K+channels

“…In addition to its crucial hormonal action to regulate cardiovascular and renal functions, angioII also acts in the central and peripheral nervous systems as a neuromodulator. Recently, angioII has been shown to augment short‐term and long‐term synaptic potentiation in sympathetic ganglia cells (Aileru et al 2004), and a role for angioII in alterations of ganglionic function in hypertensive animal models has been suggested (Yarowsky & Weinreich, 1985; Magee & Schofield, 1994). AngioII was identified early on as a potent modulator of the M current (Constanti & Brown, 1981), and M current suppression in sympathetic neurons has been shown to be mediated by AT1 receptors, G q/11 and an intracellular second messenger (Shapiro et al 1994; Haley et al 1998).…”

Alterations in Sympathetic Ganglionic Transmission in Response to Angiotensin II in (mRen2)27 Transgenic Rats

“…This is again in contrast to what we and others have seen in the ouabain-dependent rats 7 or spontaneously hypertensive animals. 8,10,[32][33][34] Bath application of Ang II enhanced the efficiency of ganglionic transmission in both groups of animals, but the enhancement was more pronounced in the (mRen2)27 rats. The concentration of Ang II was in line with that used in other in vitro studies 20 and, although above that circulating in plasma, we do not know the peptide concentration at the level of the sympathetic ganglion.…”

“…9 Presynaptically, there is enhanced release of acetylcholine. 10 Collectively, these changes in ganglionic function may contribute to increased SNA in the development and maintenance of hypertension observed in human and experimental hypertension. 11,[12][13][14][15][16][17][18][19] However, less well understood is how enhanced SNA contributes to elevated blood pressure or alters ganglionic synaptic plasticity.…”

Role of Long-Term Potentiation of Sympathetic Ganglia (gLTP) in Hypertension

“…Finally, a shift of input/output (I/O) curves of ganglia from SHR to the left side of those from young (normotensive) SHR or from WKY rats (75) indicated the expression of gLTP (58). The intercellular recording from single neurons of the SCG of SHR showed an increased amplitude of fast excitatory postsynaptic potential (EPSP) and excitatory postsynaptic potential current (EPSC) (80). This increase in EPSP and EPSC has been shown to be due to increased neurotransmitter release from presynaptic nerve terminals (80).…”

“…The intercellular recording from single neurons of the SCG of SHR showed an increased amplitude of fast excitatory postsynaptic potential (EPSP) and excitatory postsynaptic potential current (EPSC) (80). This increase in EPSP and EPSC has been shown to be due to increased neurotransmitter release from presynaptic nerve terminals (80). Thus, hypertension in the SHR has a neurogenic component that is due to the expression of gLTP in sympathetic ganglia, most probably induced by psychosocial stress.…”