Neural Sympathetic Activity in Essential Hypertension

Abstract

We read with great interest the article by Schlaich et al 1 dealing with the issue of sympathetic augmentation in hypertension. In 1993, we demonstrated that neural sympathetic activity predominance is registered in essential hypertensive patients. 2 These findings were supported by the overwhelming circulating noradrenaline (NA) versus adrenaline (Ad) levels registered throughout the oral glucose tolerance test. This NA versus Ad predominance has also been demonstrated through the supineresting/1-minute orthostasis/5-minute moderate exercise test. This test is based on the findings of Robertson et al, who demonstrated that NA, but not Ad, peaks at 1-minute orthostasis. Thus, this test allowed the investigation of both neural and adrenal sympathetic release, separately. With respect to this, we have performed this test in some 25 000 normal and diseased subjects, and the results have been published in Ͼ50 research articles and in 3 books dealing with the autonomic nervous system. 3,4 Our results might be summarized as follows: the normal NA/Ad plasma ratio is lower than 2 during the supineresting situation. This NA/Ad ratio rises to 3 to 4 in normal subjects during 1-minute orthostasis. The NA/Ad ratio does not increase, but decreases in nonessential hypertensive and/or stressed subjects, despite the global assessment that plasma catecholamines show significant increases. Conversely, essential hypertensive patients show great NA rise but none or poor Ad rise at 1-minute orthostasis. Thus, the NA/Ad ratio shows maximal increase, reaching levels Ͼ8. Plasma dopamine (DA) values do not increase in essential hypertensive patients. Thus, the NA/DA ratio shows significant rise at the 1-minute orthostasis test. The opposite NA/DA profile is registered in neurogenic hypotension. This issue should be associated with the very well-known fact that DA modulatory pool exists at sympathetic terminals, and, acting at DA-2 presynaptic inhibitory receptors, is able to regulate the NA release from those terminals. Finally, in our experience, the measurement of circulating neurotransmitters in accordance with the orthostasis test is the more accurate procedure to differentiate neural sympathetic activity from adrenal-gland sympathetic activity. The former depends on the locus coeruleus (LC) pontine-NA nucleus, and the latter is ruled directly by medullary Cl-Ad nuclei. Additional information comes from the assessment of circulating indolamines. Free-serotonin in the plasma is raised in nonessential hypertensive, but not in essential hypertensive, patients. This phenomenon correlates with the raised Ad plasma levels responsible for the increased platelet aggregation that we also find in the former group. In addition to the above, we demonstrated that Ad, but not NA, plasma level shows an absolute fall during the rapid-eyemovement sleep stage in both essential hypertensive patients and essential hypertensive rats. 4 Conversely, both NA and Ad reach almost zero values in nonessential hypertensive patients at this period. These findi...

Central Nervous System Circuitry Involved in the Hyperinsulinism Syndrome

“…These patients did not show p5HT increases. These findings suggested that the high NA plasma levels (neural sympathetic activity) registered after an oral load of glucose in hyperinsulinism patients interfered with parasympathetic activity [27, 28]. The above findings along with others obtained by our research group demonstrated that 5HT increases basal insulin release but inhibits stimulated insulin secretion (incretin effects).…”

Central Nervous System Plus Autonomic Nervous System Disorders Responsible for Gastrointestinal and Pancreatobiliary Diseases

“…The above results indicate that adrenal sympathetic and parasympathetic over neural sympathetic predominance is responsible for the hyperactivity of the enterochromaffin cells that provokes the physiological disorders underlying carcinoid syndrome and cystic fibrosis of the pancreas [15][16][17][131][132][133]. The above phenomena depend on the excitation of the C1-Ad nuclei by ACh-NTS axons [152,153].…”

Central Nervous System Circuitry and Peripheral Neural Sympathetic Activity Responsible for Essential Hypertension

“…According to these links, the (A6)-NA nucleus may provoke acute and fast bridling of the parasympathetic neurons and also indirect modulation of the adrenal sympathetic system. According to the above, although the LC-NA neurons are able to modulate BP oscillations they are not responsible for the sustained diastolic blood pressure (DBP) increase occurring in EH (Lechin et al, 1993(Lechin et al, , 2004aOgawa 1978;Sved and Felsten, 1987;Svensson 1987).…”

“…the blood, respectively. However, the LC-NA nucleus does not excite neural sympathetic activity, responsible for EH (Astier et al, 1986;Borsody 2005;Ennis and Aston-Jones, 1987;Gurtu et al, 1984;Lawler et al, 1985;Lechin et al, 1993Lechin et al, , 2004a.…”

“…The above postulation is reinforced by facts showing that the dexamethsone suppresses cortisol plasma level in non-essential hypertensive patients but not in essential hypertensive patients. (Lechin et al, 1986(Lechin et al, , 1987(Lechin et al, , 1993(Lechin et al, , 1996c(Lechin et al, , 2004a(Lechin et al, , 2006a.…”