atrial-natriuretic-factor and Cystic-Fibrosis

Regular exercise is recommended as part of cystic fibrosis (CF) physiotherapy. Exercise delays the development of pulmonary disease in CF patients; however, the cellular mechanisms responsible for these improvements are unclear. This review expands on the hypothesis that exercise improves CF pathophysiological ion dysregulation via purinergic and adrenergic pathways by describing the effects of 5' adenosine monophosphate-activated protein kinase (AMPK), atrial natriuretic peptide (ANP), and arginine-vasopressin (AVP) on CF airway epithelia. Activation of AMPK decreases Na(+) absorption, increases airway surface liquid, and reduces oxidative stress and inflammation. Plasma ANP inhibits the basolateral Na(+)/K(+)-ATPase and may therefore reduce epithelial water absorption. Airway epithelia respond to plasma AVP and secrete AVP in response to elevated bradykinin. AVP stimulates the basolateral Na(+)/K(+)/2Cl(-) exchanger, thereby increasing Cl(-) secretion, reducing Na(+) absorption, and promoting basolateral to luminal water flux. In addition, AVP may increase cilia beat frequency in airway epithelia via a Ca(2+)-dependent mechanism. This review will describe the effects of exercise on AMPK activation, ANP release, and AVP secretion; we hypothesize that the mechanical and metabolic perturbations that occur with exercise may be beneficial in preventing CF lung pathogenesis by improving airway hydration, mucociliary clearance, and reducing markers of inflammation.

Topics: AMP-Activated Protein Kinase Kinases; Arginine Vasopressin; Atrial Natriuretic Factor; Cystic Fibrosis; Epithelial Cells; Epithelium; Exercise; Humans; Male; Protein Kinases; Respiratory Mucosa; Sodium-Potassium-Exchanging ATPase

Plasma immunoreactive endothelin levels were determined in 31 children and adolescents with cystic fibrosis and it was examined whether these levels correlated with the severity of the disease. The study comprised 16 cystic fibrosis patients (mean (SD) age 13.0 (4.9) y) with impaired lung function (Group A), 15 cystic fibrosis patients (11.2 (5.5) y) with unimpaired lung function (Group B) and 28 healthy controls (10.6 (4.3) y) (Group C). The selection and classification of patients into groups was based on criteria including the grade of finger-clubbing, the Brasfield chest radiograph score and spirometric and arterial blood gas values. In all subjects, plasma immunoreactive endothelin, atrial natriuretic peptide, renin, serum aldosterone levels and serum and urine electrolytes were measured.. Plasma endothelin levels were significantly higher in Group A (range 2.5-8.4 pg/ml, median 3.2 pg/ml) than those in Group B (1.3-3.8 pg/ml, median 2.0 pg/ml, p < 0.001) and Group C (1.5-3.5 pg/ml, median 2.5 pg/ml, p < 0.001), whereas they did not differ between groups B and C. They correlated positively with the severity of finger-clubbing, heart rate, arterial blood PCO2, plasma atrial natriuretic peptide levels and serum aldosterone levels and negatively with the arterial blood PO2, forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and the Brasfield chest radiograph score. In multivariate regression analysis PO2 was the only independent factor found to significantly affect plasma endothelin levels. In conclusion, plasma immunoreactive endothelin levels are increased in cystic fibrosis patients with impaired pulmonary function and are related to the severity of the disease.

Topics: Adolescent; Atrial Natriuretic Factor; Child; Cystic Fibrosis; Endothelins; Female; Humans; Male; Prospective Studies; Respiratory Function Tests; Severity of Illness Index

Since pulmonary artery hypertension (PH) complicates advanced stages of cystic fibrosis (CF), we wondered whether plasma concentrations of h-ANP would be increased in adult patients with CF. Furthermore, if only the right ventricle is faced with an increased afterload in these patients, the increased h-ANP plasma levels should stem primarily from the right atrium. To test this hypothesis we studied 12 adult patients with CF in a clinically stable condition using right heart catheterization. Mean pressures were measured in the right atrium (Pra) and pulmonary artery (Ppa), pulmonary capillary wedge (PCWP) position, and blood were drawn from the pulmonary artery and from a peripheral vein to determine h-ANP. Plasma levels in the pulmonary artery were significantly higher than in a peripheral vein (54.3 +/- 6.0 pg/ml vs. 32.2 +/- 4.4 pg/ml; p less than 0.001). Four of the 12 patients had PH (Ppa, 25.8 +/- 2.9 mmHg) whereas 8 patients exhibited normal pulmonary artery pressures (Ppa, 15.9 +/- 0.7 mmHg). Patients with PH had higher Pra (4.2 +/- 0.4 mmHg) than patients with CF without PH (1.9 +/- 0.7 mmHg; p less than 0.05). Plasma h-ANP concentrations were significantly higher in patients with CF with PH (70 +/- 10.4 pg/ml in the pulmonary artery; 42.6 +/- 4 pg/ml in a peripheral vein) than in patients with normal pulmonary artery pressure (43 +/- 3.3 pg/ml in the pulmonary artery; p less than 0.01; 24.7 +/- 5.6 pg/ml in a peripheral vein; p less than 0.05). Although our results are derived from a small group of patients with CF, we conclude from our results that in patients with CF PH may cause increased h-ANP secretion. The right atrium seems to be a major source.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Cystic Fibrosis; Female; Humans; Hypertension, Pulmonary; Male; Pulmonary Wedge Pressure