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

Abstract

Ganglionic long-term potentiation (gLTP) is an activity-dependent sustained increase in the synaptic efficacy of the nicotinic pathway that has been demonstrated in autonomic ganglia. Sustained enhancement in ganglionic transmission as in chronic mental stress may affect the activity of autonomic functions, including blood pressure and heart rate. An increase in sympathetic activity associated with psychosocial stress and stress-prone conditions such as obesity and aging could result in in vivo expression of gLTP leading to hypertension of a neural origin. Recent reports indicated that the prevention of the expression of gLTP in animal models of hypertension prevented or reduced high blood pressure. Although stress-induced hypertension normalizes within a few days of stress relief, prolonged mild-moderate hypertension may contribute to atherosclerotic cardiovascular diseases. The relation between hypertension and enhanced ganglionic transmission as a result of in vivo expression of gLTP is discussed in this review.

Central 5-HT receptors in cardiovascular control during stress

“…7A). The history of discovery of gLTP and its properties are comprehensively covered in the introduction to the Alkahdi's seminal paper (Alkadhi et al, 1996) and in two subsequent reviews (Alkadhi et al, 2005a;Alkadhi and Alzoubi, 2007). The major contribution of these authors that is relevant to our current discussion is the discovery that activation of 5-HT3 receptors is an essential and sufficient requirement for the expression of gLTP.…”

Brain Physiology and Pathophysiology in Mental Stress

“…The function of the stress-induced elevation of blood pressure is unclear. We suggest that it may be involved in an adaptive mechanism to compensate for reduced blood perfusion reported in certain areas of the brain during stressful conditions [260,278,279].…”

“…Cushing's disease [259], hypothyroidism [15], Alzheimer's disease [50,51], and cardiovascular disease [260,261]. Longterm high concentrations of glucocorticoids will have indirect detrimental effects on the neurons, by engendering a metabolically adverse cellular environment, which increases their vulnerability to existing or impending insults such as Alzheimer's disease and Parkinson's disease [51,262].…”

“…Although stressinduced hypertension returns to normal within a few days of termination of stress, prolonged mild-moderate hypertension may contribute to atherosclerotic cardiovascular diseases [269] in addition to causing cognitive impairment [27]. Both genetic and stress-induced experimental forms of hypertension are known to include a significant neural component that contributes to the development and maintenance of this disease [260,270]. We have proposed that the stress-induced sustained increase in central sympathetic outflow to sympathetic ganglia may provide the repeated presynaptic activity required to express LTP in sympathetic ganglia, which in turn leads to a sustained increase in sympathetic tone to blood vessels, causing elevation of blood pressure [91] (see Figure 1).…”

“…In vivo expression of LTP in autonomic ganglia is expected to enhance tonic efferent signals to an array of effector organs, including the heart, blood vessels, and glands, which result in modulation of the normal physiology of these organs. We have shown that expression of ganglionic LTP, which enhances activity of the sympathetic nervous system, may be responsible for the development and/or aggravation of stress-induced hypertension in animal models (Figure 2) [91,126,260,271,[275][276][277]. Sustained elevation of sympathetic tone to the blood vessels and the heart may also lead to increased heart rate (clinically presents as palpitation) and arrhythmias, which may lead to death [277].…”