Neurohumoral Profiles Research Articles

Neurohumoral Profiles and Childhood Adversity of Patients with Multisomatoform Disorder and Pain as the Leading Bodily Symptom.

Objective Patients suffering from chronic pain often present with multifactorial underlying conditions, sometimes without concrete pathological physical findings. Functional somatic syndromes (FSS) and somatoform disorders show a high prevalence of 8-20% and are often associated with adverse childhood experiences (ACE) and chronic stress. As many different FSS have overlapping symptoms, the concept of multisomatoform disorder (MSD) has been introduced as an encompassing concept. We hypothesize that a common neurohumoral profile is present in patients with MSD that is distinct from gender- and age-matched controls and thus provides insight into possible common underlying mechanisms. Design In 151 patients with MSD (138 females) and 149 matched controls (131 females), we determined ACE by the Childhood Trauma Questionnaire (CTQ) and chronic stress by the Trier Inventory for Chronic Stress (TICS). Furthermore, the serum levels of leptin, FSH, LH, cortisol, DHEA-S, and IGF-1 have been assessed. Results There were significant differences in the levels of leptin, FSH, IGF-1, and cortisol between patients and controls, mainly driven by female participants. Levels of leptin were significantly correlated with BMI in patients, in controls, and in the female subgroup. This correlation was exaggerated in female patients when compared to female controls. Both CTQ and TICS predicted MSD directly and indirectly through the levels of leptin. Conclusion There is evidence of a distinct neurohumoral profile in female patients with MSD when compared to matched healthy controls, similar to what has been demonstrated in other chronic pain states. The observed profile can be taken as possible evidence for a dysregulated response to chronic stress and metabolic balance as well as a state of hypocortisolism and HPA-axis dysfunction. ACE and chronic stress play a major role in the development of MSD and altered neurohumoral profile.

HORMONAL AND VEGETATIVE FACTORS OF INSULIN RESISTANCE IN PATIENTS WITH HYPERTENSION

The combination of arterial hypertension (AH) and insulin resistance (IR) significantly increases the risk of cardiovascular complications. Research objective: Studying indices of carbohydrate metabolism, activity of renin-angiotensin-aldosterone system, calcium-regulating hormones, adrenal glucocorticoid function, the condition of the autonomic nervous system and their possible interrelation with hemodynamic parameters in AH patients with different insulin sensitivity. A comprehensive study of hormonal profile was held with use of radio immune method and that of central hemodynamics with use of echocardiography in 72 patients with arterial hypertension stage II, 1-2 degrees, male (mean age – 54.1±3.4 years), with a body mass index up to 30 kg / mІ and verified insulin resistance (IR), in 32 patients of which insulin resistance (IR) was revealed, and in 40 patients its absence was fixed. Insulin resistance was verified by the value of HOMA-IR in excess of 2,77. To assess the condition of the autonomic nervous system, studies of heart rate variability were performed. It is established that patients with hypertension with IR had increased level of plasma renin activity, levels of angiotensin II, cortisol, insulin, parathyroid hormone, decreased parasympathetic and increased sympathetic tonus. According to the results of factor analysis, AH with insulin resistance has a distinctive structure of neurohumoral regulation of the main indicators of central hemodynamics and interhormonal interactions; the direct regulatory effects of angiotensin II, insulin, progesterone, parathyroid hormone on the indicators of central hemodynamics, modulation of presorption action increases. The study not only revealed peculiarities of neurohumoral profiles in patients with hypertension depending on insulin resistance, but also determined distinctive features in structure of the regulatory process of central hemodynamics and interhormonal interactions. This should be taken into account when prescribing antihypertensive therapy.

Cardiopulmonary Baroreflex Control of Renal Sympathetic Nerve Activity Is Impaired in Dogs With Left Ventricular Dysfunction

Activation of neurohormonal systems contributes to the progression of heart failure (HF). The mechanism(s) whereby these systems become activated is(are) not fully explained. We determined whether vagal cardiopulmonary baroreflex control of renal sympathetic nerve activity is abnormal in dogs with left ventricular (LV) dysfunction in the absence of clinical HF, and the relationship of abnormalities in baroreflexes to the development of the neurohumoral excitatory state. LV end-systolic and end-diastolic dimensions (echocardiography), arterial baroreflex sensitivity (slope of ΔRR/Δsystolic BP during phenylephrine or nitroglycerin bolus), and neurohumoral profiles (plasma norepinephrine, renin activity, and arginine vasopressin) were measured serially in conscious dogs (n=24) with progressive LV dysfunction due to rapid ventricular pacing. LV dimensions were used to define groups with mild, moderate, and marked LV dilatation (LVD; increase in LV end-diastolic volume <15%, 15-30%, and >30% of control, respectively). Changes in renal nerve activity (RNA) were recorded in response to increases in pulmonary capillary wedge pressure (PCWP) induced by volume infusion in anesthetized, sinoaortic-denervated dogs. Cardiopulmonary baroreflex sensitivity (slope of %ΔRNA/ΔPCWP) for mild LVD (-17.8%/mmHg) was the same as controls (-17.7%/mmHg). However, the slopes of moderate (-5.8%/mmHg) and severe LVD (-1.9%/mmHg) were decreased significantly compared with controls (P < .05). Arterial baroreflex sensitivity was preserved at all stages of LVD. Plasma norepinephrine, renin activity, and arginine vasopressin remained unchanged after 4, 7, and 11 days of pacing. Vagal cardiopulmonary baroreflex control of renal sympathetic nerve activity is blunted early in the development of LVD. These abnormalities precede neurohumoral excitation and abnormal arterial baroreflexes and become apparent when LV end-diastolic volume starts to increase.

Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral profiles toward the goal of selecting more focused and mechanistic-based treatment options for pediatric patients with OI.

Utility of neurohumoral profiles in pulmonary hypertension: clinical and hemodynamic correlations

Utility of neurohumoral profiles in pulmonary hypertension: clinical and hemodynamic correlations

Treatment of Heart Failure With Fosinopril: An Angiotensin Converting Enzyme Inhibitor With a Dual and Compensatory Route of Excretion

Congestive heart failure (CHF) is one of the most common and clinically important cardiovascular diseases. This pathologic state is characterized not only by well-defined hemodynamic alterations, but also by complex abnormalities involving the sympathetic nervous system, the renin-angiotensin system, and other hormones involved in cardiovascular homeostasis. In addition, there is an abnormality in the homeostatic cardiovascular control exerted by arterial baroreceptors and the viscoelastic properties of medium-size arteries are altered, causing a reduction in arterial compliance. All of these abnormalities can be favorably affected by angiotensin converting enzyme (ACE) inhibitors, which have been shown to improve not only the hemodynamic and neurohumoral profiles of CHF, but also patient survival. CHF is accompanied with a decline or some sort of effect on renal function. An ACE inhibitor with a dual route of excretion, such as fosinopril, may be especially useful in treating patients with CHF.

Ischemic versus idiopathic cardiomyopathy: differing neurohumoral profiles despite comparable peak oxygen uptake

Objective: We tested the hypothesis that neurohormonal and immunological activation differs in ischemic and idiopathic dilated cardiomyopathy since recent intervention trials indicate that ischemic cardiomyopathy seems to carry a worse prognosis than idiopathic cardiomyopathy of comparable clinical severity. Methods: In ten patients with ischemic cardiomyopathy undergoing spiroergometric evaluation venous levels of norepinephrine, epinephrine, renin, angiotensin, atrial natriuretic peptide as well as soluble interleukin-2-receptor were determined before, during and 10 min after exercise. Results were compared to sixteen patients with idiopathic cardiomyopathy with similar peak oxygen uptake (13.3±3 vs. 13.6±3 ml/kg/min; P=ns). Results: In ischemic patients, norepinephrine, angiotensin, and interleukin-2 receptor levels were significantly higher before, during and after exercise. Interleukin-2-receptor levels correlated with angiotensin. Conclusions: We conclude that in ischemic as compared to idiopathic cardiomyopathy, a more pronounced activation of the sympathetic, renin–angiotensin and T-cell immune system is present at rest, during and after exercise. These data may contribute to explain differences in response to intervention and in prognosis. They warrant further investigation.

Treatment with enalapril fails to prevent impaired cardiopulmonary baroreflex control in dogs with left ventricular dysfunction

That the cardiopulmonary baroreflex control of sympathetic nerve activity is impaired in dogs with left ventricular (LV) dysfunction has been shown previously. This study tested the hypothesis that treatment with the angiotensin-converting enzyme inhibitor enalapril prevents or delays the development of abnormalities of cardiopulmonary baroreflexes in dogs with LV dysfunction. Serial changes in LV volumes and neurohumoral profiles (plasma norepinephrine and renin activity) were assessed in conscious dogs with progressive LV dysfunction due to rapid ventricular pacing. Enalapril 5 mg orally twice daily was administered from days 4 to 12 of pacing. Cardiopulmonary baroreflexes were assessed in enalapriltreated paced dogs (n = 8) and untreated paced dogs (n = 8) by recording changes in renal nerve activity and pulmonary capillary wedge pressure during volume infusion in anesthetized sinoaortic denervated dogs on day 12 of rapid pacing. There was no difference in LV volume in the two groups. Neurohumoral factors were similar in both groups except for the expected high plasma renin activity in enalapril-treated dogs. Hemodynamic parameters also were comparable in the two groups. Cardiopulmonary baroreflex sensitivity for enalapriltreated dogs was not different from that of untreated paced dogs, and baroreflex gain in both groups was significantly lower than for the nonpaced control dogs ( P < .05). Despite adequate converting enzyme blockade, treatment with enalapril failed to prevent the development of attenuated cardiopulmonary baroreflex control of sympathetic nerve activity in dogs with developing LV dysfunction.

Effects of beta-blockade on neurohumoral responses and neurochemical markers in pacing-induced heart failure.

We investigated neurohumoral profiles and transmitter and neuroenzyme markers of cardiac autonomic innervation in control (unpaced) dogs and three groups of dogs with pacing-induced heart failure (paced, paced + beta-adrenergic blockade, and paced + cardiac denervation). Left ventricular ejection fraction decreased significantly and to a comparable extent in all paced groups. Pacing increased plasma norepinephrine (NE); increases in NE were not attenuated but instead tended to be exaggerated by treatment with propranolol or cardiac denervation. Atrial hypertrophy occurred in all paced groups compared with the control group. However, atrial and right ventricular hypertrophy were not as pronounced in the paced plus cardiac denervation group as in the paced and paced plus propranolol groups. Pacing also depleted neuropeptide Y and NE from all heart chambers; propranolol treatment did not modify these local tissue changes. Pacing caused selective depletion of neuroenzymes predominantly in the left ventricle; again, propranolol did little to modify these changes. In this study of paced animals with experimentally maintained cardiac dysfunction, failure to modify noradrenergic responses with intrapericardial cardiac denervation suggests that noncardiac sources contribute predominantly to high plasma NE. Failure to modify neurohumoral, neuropeptide, and neuroenzyme responses with beta-antagonist suggests this treatment has little practical direct influence on sympathetic vasomotor activity or neuronal function in heart failure.

Selective activation of atrial natriuretic peptide in patients with myocardial infarction and mild left ventricular dysfunction

The purpose of this study was to investigate whether neurohumoral activation occurs in asymptomatic patients with acute myocardial infarction (AMI) and without clinical signs of heart failure. During the early phase of AMI (mean 8 days), the neurohumoral profiles of 60 patients (mean age 59 range 37 to 70) were examined. Blood levels of the following humoral parameters were measured: atrial natriuretic peptide (ANP), plasma renin activity, aldosterone and vasopressin. All patients underwent cardiac catheterization during hospitalization. Baseline hemodynamic characteristics identified left ventricular dysfunction (ejection fraction ≤45% and/or left ventricular end-diastolic pressure ≥15 mmHg) in 32 patients; the remaining 28 patients had normal hemodynamic parameters. In patients with AMI, plasma ANP levels differed significantly from control subjects (111 ± 74 pg/ml vs. 53 ± 18 pg/ml; P < 0.001). In patients with AMI and mild left ventricular dysfunction ANP levels were significantly increased when compared to patients with AMI and normal left ventricular function (129 ± 73 pg/ml vs. 82 ± 69 pg/ml; P < 0.001). The hemodynamic data showed a significant correlation with ANP only in patients with AMI and left ventricular dysfunction (EF% r = 0.42; LVEDP r = 0.44; P < 0.001). These data show that in patients with myocardial infarction and without heart failure, the atrial natriuretic peptide is the only neurohumoral system activated out of all neurohumoral systems tested in this population and its circulating levels are strictly related to the degree of left ventricular dysfunction.

Role of left ventricular dysfunction in neurohumoral activation in the recovery phase of anterior wall acute myocardial infarction

Neurohumoral activation is readily apparent in patients with symptomatic congestive heart failure (CHF) and in the acute phase after acute myocardial infarction. In this study, the neurohumoral profiles of 36 asymptomatic patients in the early convalescent phase after acute myocardial infarction were examined. All patients in the study had a radionuclide ejection fraction ≤45% and underwent cardiac catheterization 11 to 30 days after infarction. Venous blood samples were obtained in the supine state for the measurement of norepinephrine, angtotensin II, plasma renin activity and aldosterone in all patients. Despite the reduced ejection fraction and extensive wall motion abnormalities, plasma norepinephrine was not elevated and did not correlate with any measured hemodynamic, angiographic or clinical variables. The renin-angiotensin II aldosterone system was activated, as expected, in the 9 study patients receiving loop diuretics. However, even in the 27 patients not taking diuretics, plasma angiotensin II and renin activity levels were increased in relation to Killip classification, the presence of a left ventricular (LV) aneurysm and LV ejection fraction. Activation of the renin-angiotensin-aldosterone system can be identified in hemodynamically compensated postinfarction patients not taking diuretics and appears to be related to the extent of LV dysfunction.