For circulating norepinephrine (NE) to reflect sympathetic activity validly, plasma NE should show an intensity-dependent increase during sympathetic stimulation and decrease during sympathetic inhibition, and circulating NE should correlate with more directly obtained measures of sympathetic activity. Review of published evidence indicates that NE in peripheral plasma satisfies these criteria. However, models used to explain the relationship between circulating NE and sympathetic activity must take into account processes intervening between the synaptic cleft and free NE in the circulation and, since sympathetic outflow is regionalized, the contributions of specific vascular beds to circulating NE. In this report a model is presented where removal processes for NE are viewed as acting in series to produce a gradient in NE concentrations from synapse to plasma, and where the relative contributions of specific vascular beds are calculated from the arteriovenous difference in plasma NE across those beds and the percentage of cardiac output distributed to them. In general, venous plasma NE provides a useful estimation of average sympathetic outflow.

Relationship between plasma norepinephrine and sympathetic neural activity

We studied the responses of plasma CRH, ACTH, cortisol, norepinephrine, epinephrine, and renin activity in 11 patients undergoing parathyroid or thyroid surgery after identical preoperative sedation and during isoflurane (Forane) anesthesia. During surgical exploration, plasma CRH levels [10 +/- 2 (+/- SEM) pg/mL] remained at basal (unstimulated) levels, and plasma ACTH (11.5 +/- 1.4 pg/mL), cortisol (24 +/- 4 micrograms/dL), and epinephrine (35 +/- 10 pg/mL) concentrations remained within their normal morning ranges. The majority of the patients had no evidence of pulsatile ACTH secretion during the operation, but, rather, secreted ACTH and cortisol continuously. There was a small elevation of plasma norepinephrine and PRA which was associated with a small increase in heart rate and decrease in blood pressure. Anesthesia reversal, endotrachial extubation, and the early recovery period were associated with marked mean peak increases in plasma ACTH (173 +/- 45 pg/mL), cortisol (35 +/- 6 micrograms/dL), and epinephrine (220 +/- 56 pg/mL) and the return of plasma norepinephrine and PRA to basal levels. All hormones returned to basal levels by the first post-operative day. The data suggest that with modern anesthetic techniques patients undergoing neck surgery had mildly elevated plasma ACTH, cortisol, and epinephrine levels. Glucocorticoid secretion during the operation was maintained primarily by continuous rather than pulsatile ACTH secretion. The immediate postoperative period was associated with profound elevations of plasma ACTH, cortisol, and epinephrine. The major determinant of ACTH, cortisol, and epinephrine secretion was anesthesia reversal and recovery and not surgical trauma.

Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress.

Physical challenges, emotional arousal, increased physical activity, or changes in the environment can evoke stress, requiring altered activity of visceral organs, glands, and smooth muscles. These alterations are necessary for the organism to function appropriately under these abnormal conditions and to restore homeostasis. These changes in activity comprise the "fight-or-flight" response and must occur rapidly or the organism may not survive. The rapid responses are mediated primarily via the catecholamines, epinephrine, and norepinephrine, secreted from the adrenal medulla. The catecholamine neurohormones interact with adrenergic receptors present on cell membranes of all visceral organs and smooth muscles, leading to activation of signaling pathways and consequent alterations in organ function and smooth muscle tone. During the "fight-or-flight response," the rise in circulating epinephrine and norepinephrine from the adrenal medulla and norepinephrine secreted from sympathetic nerve terminals cause increased blood pressure and cardiac output, relaxation of bronchial, intestinal and many other smooth muscles, mydriasis, and metabolic changes that increase levels of blood glucose and free fatty acids. Circulating catecholamines can also alter memory via effects on afferent sensory nerves impacting central nervous system function. While these rapid responses may be necessary for survival, sustained elevation of circulating catecholamines for prolonged periods of time can also produce pathological conditions, such as cardiac hypertrophy and heart failure, hypertension, and posttraumatic stress disorder. In this review, we discuss the present knowledge of the effects of circulating catecholamines on peripheral organs and tissues, as well as on memory in the brain.

Peripheral and central effects of circulating catecholamines.

Background and Purpose— Sympathetic hyperactivity is a contributing cause of vascular disorders because it increases blood pressure, blood sugar, and blood lipids. Pervasive compromise of the central and peripheral autonomic nervous systems is common in idiopathic Parkinson disease (IPD) resulting in reduced sympathetic and parasympathetic function. We hypothesized that IPD was associated with reduced prevalence of cardiovascular disease risk factors as a result of reduced sympathetic activity. Methods— We performed a retrospective case-control study on 178 newly diagnosed consecutive IPD patients, and 533 age- (±3 years) and sex-matched controls with other neurological diseases seen over the same period at the same hospital. For each case and control the following were noted on admission: smoking, diabetes, hypertension, body mass index, serum glucose, plasma cholesterol, triglycerides and total lipid levels, and blood pressure. Results— Diabetes, history of smoking, high blood pressure, high blood gluco...

Reduced Risk Factors for Vascular Disorders in Parkinson Disease Patients A Case-Control Study

Plasma ACTH and cortisol concentrations are frequently elevated in patients in intensive care units (ICU). To examine the functional integrity of the hypothalamic-pituitary-adrenal axis during critical illness, we evaluated prospectively 53 ICU patients in a general medical ICU. Thirty-one patients and 7 normal controls underwent an overnight dexamethasone suppression test (3 mg dexamethasone, orally, at 2300 h). Plasma ACTH and serum cortisol were measured at 0900 h. In a separate experiment, 22 patients and 7 control subjects underwent a CRH stimulation test [100 micrograms human (h) CRH, iv]. ACTH and cortisol concentrations were determined from -15 to 120 min. Compared to normal controls, plasma ACTH and serum cortisol concentrations were not fully suppressible by dexamethasone [mean +/- SEM: plasma ACTH, 21 +/- 4 vs. 3 +/- 0.5 pg/mL (4.7 +/- 0.9 vs. 0.7 +/- 0.1 pmol/L); serum cortisol, 13.9 +/- 1.9 vs. 1.5 +/- 0.3 micrograms/dL (390 +/- 50 vs. 40 +/- 10 nmol/L); P = 0.0001], demonstrating an altered glucocorticoid feedback in the ICU patients. Patients undergoing hCRH stimulation had clearly elevated mean baseline plasma ACTH and serum cortisol concentrations [ACTH, 78 +/- 20 pg/mL vs. 15 +/- 3 in controls (17.2 +/- 4.4 vs. 3.4 +/- 0.7 pmol/L; P = 0.007); cortisol, 36.8 +/- 3.4 micrograms/dL vs. 9.6 +/- 1.2 (1020 +/- 80 vs. 260 +/- 30 nmol/L; P = 0.0001)]. Despite elevated baseline glucocorticoid concentrations, stimulation with hCRH resulted in significantly higher peak plasma ACTH concentrations 15 min after hCRH than in controls [134 +/- 31 vs. 48 +/- 9 pg/mL (29.5 +/- 6.8 vs. 10.6 +/- 2.0 pmol/L); P < 0.05]. Serum cortisol concentrations in ICU patients were significantly elevated throughout the test period (P = 0.0001) and rose to a peak of 43.9 +/- 3.5 micrograms/dL compared to 18.2 +/- 2.0 micrograms/dL in controls (1210 +/- 70 vs. 500 +/- 60 nmol/L). We conclude that ICU patients have a markedly altered responsiveness of their pituitary corticotroph to suppression with dexamethasone and stimulation with hCRH. These findings may be explained by altered pituitary glucocorticoid feedback and/or hypersecretion of peptides with CRH-like activity (vasopressin and cytokines) during critical illness.

https://epub.ub.uni-muenchen.de/7007/1/Reincke_Martin_7007.pdf

The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone.

Epinephrine (E), norepinephrine (NE), dopamine (DA) and Cortisol (F) were measured in samples drawn simultaneously by direct venepuncture from the brachial and the adrenal vein of 12 patients undergoing surgery for left kidney diseases. In 7 patients the influence of anesthesia on peripheral plasma levels was also assessed. Catecholamines were measured by a radioenzymatic assay and F by radioimmunoassay. Compared to basal values (mean ± SE) (E: 53.6 ± 6.2 pg/ml; NE: 209.4 ± 24.4 pg/ml; DA: 24.5 ± 3.3 pg/ml; F: 12.9 ± 1.2 μg/dl) only NE peripheral levels were significantly modified by anesthesia (NE: 343.7 ± 67.4 pg/ml p < 0.05), whereas under surgery a significant increase in the peripheral levels was found for every substance measured (mean ± SE) (E: 332.5 ± 46.6 pg/ml p < 0.001; NE: 633.6 ± 114.2 pg/ml p < 0.005; DA: 85.8 ± 15.7 pg/ml p < 0.005; F:21.3 ± 1.9 μ/dl p < 0.01). Catecholamine and F levels in adrenal vein showed a high variability suggesting an intermittent secretion. In the adrenal venous blood E levels were, in the mean, 381 times higher, NE levels 45 times, DA levels 27 times and F levels 23 times higher than in peripheral blood. E, NE and DA concentrations in the adrenal vein were all significantly correlated to the others but not to Cortisol, suggesting that the medulla secrets E, NE and DA in rather constant ratios and that the cortex and the medulla respond differently to surgical stress.

A study on human adrenal secretion. Measurement of epinephrine, norepinephrine, dopamine and Cortisol in peripheral and adrenal venous blood under surgical stress

D. Turini

Papers

A study on human adrenal secretion. Measurement of epinephrine, norepinephrine, dopamine and Cortisol in peripheral and adrenal venous blood under surgical stress