endothelin-1 and Hyperventilation

We studied the contributions of hypoxemia, hypocapnia, and hyperpnea to the acute hypoxic diuretic response (HDR) in humans and evaluated the role of peripheral O(2) chemosensitivity and renal hormones in HDR. Thirteen healthy male subjects (age 19-38 yr) were examined after sodium equilibration (intake: 120 mmol/day) during 90 min of normoxia (NO), poikilocapnic hypoxia (PH), and isocapnic hypoxia (IH) (days 1-3, random order, double blind), as well as normoxic voluntary hyperpnea (HP; day 4), matching ventilation during IH. O(2) saturation during PH and IH was kept equal to a mean level measured between 30 and 90 min of breathing 12% O(2) in a pretest. Urine flow during PH and IH (1.81 +/- 0.92 and 1.94 +/- 1.03 ml/min, respectively) but not during HP (1.64 +/- 0.96 ml/min) significantly exceeded that during NO (control, 1.38 +/- 0.71 ml/min). Urine flow increases vs. each test day's baseline were significant with PH, IH, and HP. Differences in glomerular filtration rate, fractional sodium clearance, urodilatin, systemic blood pressure, or leg venous compliance were excluded as factors of HDR. However, slight increases in plasma and urinary endothelin-1 and epinephrine with PH and IH could play a role. In conclusion, the early HDR in humans is mainly due to hypoxia and hypocapnia. It occurs without natriuresis and is unrelated to O(2) chemosensitivity (hypoxic ventilatory response).

Topics: Adult; Atrial Natriuretic Factor; Blood Gas Analysis; Blood Pressure; Carbon Dioxide; Catecholamines; Diuresis; Double-Blind Method; Endothelin-1; Heart Rate; Hormones; Humans; Hyperventilation; Hypocapnia; Hypoxia; Kidney; Kidney Function Tests; Male; Natriuresis; Oxygen; Partial Pressure; Peptide Fragments; Pulmonary Ventilation; Sodium; Time Factors; Urodynamics

The purpose of the study was to investigate whether provoked changes of cerebral perfusion pressure and arterial carbon dioxide tension are able to influence the cerebral metabolism of endothelin-1 (ET-1) in a porcine model. Brain tissue oxygen tension, regional cerebral blood flow and mean arterial blood pressure were monitored in 10 healthy pigs during induced hyperventilation (HV), hypertension (HrT) and hypotension (HoT). ET-1 was determined in the arterial and cerebrovenous blood. Microdialysis samples (lactate, glucose and pyruvate) were taken from brain and subcutaneous tissue. A significant decrease (p<0.05) of the arterial ET-1 (1.46+/-0.33 fmol/mL) compared to the baseline (2.18+/-0.36 fmol/mL) was observed after the HoT-period. We detected a positive correlation between cerebrovenous ET-1 and extracellular cerebral glucose (0.68; p<0.05) after the baseline as well as a negative correlation of -0.81 (p<0.005) between the cerebrovenous ET-1 level and the extracellular cerebral lactate after the HoT-period. These data imply that with increasingly pathological changes of the cerebral metabolism endothelin becomes progressively more important in the regulation of cerebral vascular tone.

Topics: Animals; Blood Circulation Time; Blood Glucose; Cerebrovascular Circulation; Disease Models, Animal; Endothelin-1; Extracellular Fluid; Hypertension; Hyperventilation; Hypotension; Intracranial Pressure; Lactates; Microdialysis; Regional Blood Flow; Swine; Time Factors

Nitric oxide (NO)/endothelin imbalance may play a role in the regulation of cerebral blood flow. The aim of the present study was to assess whether these endothelial factors influence middle cerebral artery blood flow velocities (MCAV) and cerebrovascular reactivity (CVR) in healthy and hypertensive adolescents.. 106 adolescents (61 hypertensive and 45 normotensive) underwent transcranial Doppler measurements of the middle cerebral artery at rest and after 30 s of breath-holding (BH) and 60 s of hyperventilation (HV). Additionally, NO and endothelin-1 (ET-1) concentrations of the serum were assessed. The correlation between NO and ET-1 levels as well as MCAV and CVR values was analyzed.. Resting MCAVs were higher among hypertensive teenagers (76.5 +/- 24 vs. 62.8 +/- 15.6 cm/s, respectively, p < 0.001). CVR values did not differ between hypertensive and healthy adolescents after the BH and HV procedure. A significant negative correlation was found between absolute MCAV values and NO concentrations. ET-1 was positively related to MCAV.. Cerebral blood flow velocities, but not CVR values, are associated with serum NO and ET-1 concentrations in adolescents.

Topics: Adolescent; Analysis of Variance; Blood Flow Velocity; Blood Pressure; Brain; Endothelin-1; Female; Humans; Hypertension; Hyperventilation; Hypocapnia; Male; Middle Cerebral Artery; Nitric Oxide; Ultrasonography, Doppler, Transcranial