digoxin and Hypoventilation

This article reviews evidence that mild, but sustained, inhibition of breathing can affect blood pressure regulation via effects of increased PCO2 on sodium regulation. Experiments with micropigs are summarized which show that anticipation of the onset of a familiar avoidance task is accompanied by sustained increases in PCO2, increases in plasma hydrogen and bicarbonate ion concentrations, decreases in hematocrit, and increases in circulating levels of sodium pump inhibitors that are sensitive to plasma volume. Observational studies with humans using an ambulatory respiration monitor characterize episodes of inhibited breathing occurring in the natural environment. Experimental studies with human subjects show that voluntary maintenance of end-tidal CO2 near the upper end of the normal range results in decreases in renal sodium excretion, increases in plasma sodium pump inhibitors and inhibition of sodium pump activity. Together, these studies are consistent with the view that behavioral stress can influence blood pressure regulation via sustained inhibition of respiration which acidifies the plasma and increases sodium/hydrogen exchange in kidneys and blood vessels.

Topics: Arousal; Blood Pressure; Cardenolides; Digoxin; Humans; Hypercapnia; Hypoventilation; Kidney; Neural Inhibition; Psychophysiology; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase

Previous studies with micropigs showed that conditioned suppression of respiration preceding the onset of an avoidance task was associated with increased pCO2, decreased plasma pH, decreased hematocrit, and increased blood pressure with no change in heart rate. Voluntary hypoventilation by humans, which evoked similar effects, was found to elicit increases in plasma endogenous digitalis-like factors (EDLF) and decreases in erythrocyte Na,K-ATPase. The present study investigated plasma EDLF and Na,K-ATPase activity in micropigs preceding and during avoidance sessions. Compared with levels in a controlled environment, 1 h of quiet waiting for the onset of a 30-min avoidance task was associated with hypoventilation, acidification of the plasma, and a decrease in hematocrit with progressive increases in plasma EDLF, and decreased in erythrocyte Na,K-ATPase activity (1.67 +/- 0.35 v 2.73 +/- 0.24 mumol Pi/mL er/h). Systolic blood pressure increased (126.5 +/- 5.7 v 121.7 +/- 4.2 mm Hg) during preavoidance periods, with no changes in heart rate (89.5 +/- 3.9 v 89.4 +/- 4.0 beats/min). During the avoidance sessions, plasma EDLF, systolic blood pressure (126.7 +/- 4.5 mm Hg), and heart rate (107.3 +/- 4.8 beats/min) were elevated above the first 10 min of preavoidance, whereas Na,K-ATPase activity returned toward control values (2.46 +/- 0.83 mumol Pi/mL er/h). These findings are consistent with the view that elevation of blood pressure during behaviorally induced hypoventilation in micropigs is mediated in part by inhibition of Na,K-ATPase by increases in plasma EDLF due to expanded plasma volume.

Topics: Animals; Avoidance Learning; Bicarbonates; Blood Pressure; Cardenolides; Digoxin; Erythrocytes; Heart Rate; Hematocrit; Hydrocortisone; Hydrogen-Ion Concentration; Hypoventilation; Oxygen; Potassium; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase; Swine; Swine, Miniature

Topics: Brain Diseases; Chemoreceptor Cells; Chronic Disease; Diagnosis, Differential; Diazepam; Digoxin; Furosemide; Humans; Hydrochlorothiazide; Hypercapnia; Hypoventilation; Hypoxia; Lung Diseases, Obstructive; Male; Obesity; Respiratory Center; Respiratory Function Tests