VASOPRESSIN AND OXYTOCIN RELEASE DURING PROLONGED ENVIRONMENTAL HYPOXIA IN THE RAT

Background - The mechanism causing peripheral oedema in hypoxaemic chr onic obstructive pulmonary disease has not been established. Vasopress in, a powerful antidiuretic hormone involved in salt and water homeost asis, is released in response to acute hypoxia. However, the effect of prolonged hypoxaemia on hypothalamic and pituitary release of the mag nocellular hypothalamic hormones, vasopressin and oxytocin, has not pr eviously been studied. Methods - Male Wistar rats were randomly alloca ted to either normobaric, hypoxic (10% O-2) Or control (21% O-2) envir onmental chambers. An initial series of experiments examined plasma va sopressin concentration, osmolality, sodium concentration, packed cell volume (PCV), and weight gain at weekly intervals (n=4-6) for six wee ks. The maximum increase in plasma vasopressin concentration and PCV o ccurred after five weeks. In a second experiment vasopressin and oxyto cin concentrations in the hypothalamus, pituitary gland, and plasma we re measured in eight control and eight hypoxic rats after five weeks i n the environmental chambers. Results - In rats exposed to environment al hypoxia PCV increased (p<0.001) and weight gain decreased (p<0.05) compared with controls. The plasma vasopressin concentration increased progressively from a baseline of 1.36 (0.2) pmol/l (n=6) to a maximum of 4.38 (0.8) pmol/l (n=6; p<0.01) during the first five weeks of env ironmental hypoxia (difference 3.02 (95% CI 1.18 to 4.86)). Plasma osm olality and sodium concentration were unchanged in hypoxic rats compar ed with controls during the six week period. The hypothalamic vasopres sin concentration was increased (p<0.001) after five weeks of environm ental hypoxia (91.6 (4.8) pmol/l hypothalamus) compared with controls (57.4 (5.1) pmol/hypothalamus), the difference being 34.2 pmol/hypotha lamus (95% CI 21.6 to 46.5). The pituitary vasopressin concentration w as unchanged. In hypoxic rats hypothalamic oxytocin (59.6 (3.2) pmol/h ypothalamus) was greater (p<0.01) than in controls (42 (3.8) pmol/hypo thalamus), a difference of 17.6 pmol/hypothalamus (95% CI 8.7 to 26.5) . Similarly, the plasma oxytocin concentration was increased (p<0.05) in hypoxic rats (6.78 (1.2) pmol/l) compared with controls (3.3 (0.8) pmol/l), a difference of 3.48 pmol/l (95% CI 0.89 to 6.07). The pituit ary oxytocin concentration was unchanged in the two groups. Conclusion s - These results demonstrate an increase in hypothalamic production o f vasopressin and oxytocin in rats during prolonged hypoxaemia. Increa sed plasma concentrations of neurohypophysial hormones would be expect ed to impair sodium and water homeostasis in patients with hypoxaemia. However, the absence of change in the plasma osmolality and sodium co ncentrations in this study and previous clinical investigations sugges ts that compensatory mechanisms modulate the actions of both vasopress in and oxytocin. A reduction in renal blood flow or decreased renal re sponsiveness to the neurohypophyseal hormones may be involved.