The sympathetic nervous system is an important regulator of blood pressure Guyenet describes the central control regions that influence the activity of sympathetic efferent neurons and their potential contribution to neurogenic hypertension Hypertension — the chronic elevation of blood pressure — is a major human health problem In most cases, the root cause of the disease remains unknown, but there is mounting evidence that many forms of hypertension are initiated and maintained by an elevated sympathetic tone This review examines how the sympathetic tone to cardiovascular organs is generated, and discusses how elevated sympathetic tone can contribute to hypertension

The sympathetic control of blood pressure

We examined the subnuclear organization of projections to the parabrachial nucleus (PB) from the nucleus of the solitary tract (NTS), area postrema, and medullary reticular formation in the rat by using the anterograde and retrograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and anterograde tracing with Phaseolus vulgaris-leucoagglutinin. Different functional regions of the NTS/area postrema complex and medullary reticular formation were found to innervate largely nonoverlapping zones in the PB. The general visceral part of the NTS, including the medial, parvicellular, intermediate, and commissural NTS subnuclei and the core of the area postrema, projects to restricted terminal zones in the inner portion of the external lateral PB, the central and dorsal lateral PB subnuclei, and the "waist" area. The dorsomedial NTS subnucleus and the rim of the area postrema specifically innervate the outer portion of the external lateral PB subnucleus. In addition, the medial NTS innervates the caudal lateral part of the external medial PB subnucleus. The respiratory part of the NTS, comprising the ventrolateral, intermediate, and caudal commissural subnuclei, is reciprocally connected with the Kolliker-Fuse nucleus, and with the far lateral parts of the dorsal and central lateral PB subnuclei. There is also a patchy projection to the caudal lateral part of the external medial PB subnucleus from the ventrolateral NTS. The rostral, gustatory part of the NTS projects mainly to the caudal medial parts of the PB complex, including the "waist" area, as well as more rostrally to parts of the medial, external medial, ventral, and central lateral PB subnuclei. The connections of different portions of the medullary reticular formation with the PB complex reflect the same patterns of organization, but are reciprocal. The periambiguus region is reciprocally connected with the same PB subnuclei as the ventrolateral NTS; the rostral ventrolateral reticular nucleus with the same PB subnuclei as both the ventrolateral (respiratory) and medial (general visceral) NTS; and the parvicellular reticular area, adjacent to the rostral NTS, with parts of the central and ventral lateral and the medial PB subnuclei that also receive rostral (gustatory) NTS input. In addition, the rostral ventrolateral reticular nucleus and the parvicellular reticular formation have more extensive connections with parts of the rostral PB and the subjacent reticular formation that receive little if any NTS input. The PB contains a series of topographically complex terminal domains reflecting the functional organization of its afferent sources in the NTS and medullary reticular formation.

Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat.

Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

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Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.

Efferent projections of the infralimbic cortex of the rat.

During stress, the activity of the sympathetic nervous system is changed in a global fashion, leading to an increase in cardiovascular function and a release of adrenal catecholamines. This response is thought to be regulated by a common set of brain neurons that provide a dual input to the sympathetic preganglionic neurons regulating cardiac and adrenal medullary functions. By using a double-virus transneuronal labeling technique, the existence of such a set of central autonomic neurons in the hypothalamus and brainstem was demonstrated. These neurons innervate both of the sympathetic outflow systems and likely function in circumstances where parallel sympathetic processing occurs, such as in the fight-or-flight response.

https://science.sciencemag.org/content/sci/270/5236/644.full.pdf

Central Command Neurons of the Sympathetic Nervous System: Basis of the Fight-or-Flight Response

We have studied the responses to electrical and chemical stimulation of the ventrolateral medulla in the chloralose-anesthetized, paralyzed, artificially ventilated rat Locations of most active pressor responses were compared to regions containing neurons labeled immunocytochemically for phenylethanolamine N-methyltransferase (PNMT), the enzyme catalyzing the synthesis of adrenaline Elevations of arterial pressure (+816 +/- 25 mm Hg) and cardioacceleration (+73 +/- 136 bpm) were elicited with low current (5 times threshold of 95 +/- 11 microA) electrical stimulation in a region of rostral ventrolateral medullary reticular formation we have termed the nucleus reticularis rostroventrolateralis (RVL) Electrical stimulation of the RVL increased plasma catecholamines (168-fold for adrenaline, 53-fold for noradrenaline, and 19-fold for dopamine) and vasopressin (17-fold before spinal transection, 47-fold after) The location of the most active pressor region in the ventrolateral medulla corresponded closely with the location of C1 adrenaline-synthesizing (PNMT-containing) neurons In addition, the location of the most active pressor region in the dorsomedial medulla corresponded with the location of a bundle of PNMT-containing axons Unilateral injections into the RVL of the excitatory amino acid monosodium L-glutamate (50 pmol to 10 nmol), but not saline, caused transient dose-dependent and topographically specific elevations (maximum +716 +/- 49 mm Hg) of arterial blood pressure and tachycardia Injections of the rigid structural analogue of glutamate, kainic acid, caused large, prolonged (at least 15 min) pressor responses and tachycardia Unilateral injections of the inhibitory amino acid gamma-aminobutyric acid (GABA) into the RVL caused transient dose-dependent hypotension (maximum -408 +/- 66 mm Hg) and bradycardia, whereas the specific GABA antagonist bicuculline caused prolonged (10 to 20 min) elevations (+642 +/- 68 mm Hg) of arterial pressure and tachycardia By contrast, injections of the glycine antagonist strychnine had no significant effect Bilateral injections of the neurotoxin, tetrodotoxin, dropped arterial pressure to low levels (517 +/- 47) not changed by subsequent spinal cord transection at the first cervical segment (525 +/- 62) We propose the following (1) Neurons within the RVL, most probably C1 adrenaline-synthesizing neurons, exert an excitatory influence on sympathetic vasomotor fibers, the adrenal medulla, and the posterior pituitary (2) These neurons are tonically active and under tonic inhibitory control, in part via GABAergic mechanisms--perhaps via the nucleus of the solitary tract (NTS)(ABSTRACT TRUNCATED AT 400 WORDS)

https://www.jneurosci.org/content/jneuro/4/2/474.full.pdf

Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin

Juan M. Saavedra

Papers

Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin