Dexamethasone potentiates hypoxic vasoconstriction in salt solution-perfused rat lungs.
Isolated rat lungs perfused with blood or plasma develop good hypoxic pressor reactivity, but those flushed of blood and perfused solely with physiological salt solution (PSS) show decreased or no hypoxic vasoconstriction. Because the handling of rats during collection of blood increases the plasma corticosterone levels, we wondered whether the difference between blood and PSS perfusion was due partly to higher glucocorticoid activity with blood than with PSS. Treatment of lung donors with the synthetic glucocorticoid dexamethasone (2 mg/kg im 3 h before isolation) or addition of dexamethasone (4.2 X 10(-6) M) to the perfusate increased markedly the hypoxic pressor reactivity of rat lungs perfused with PSS plus albumin (4 g/100 ml). In comparison, dexamethasone did not cause a significant increase in the already vigorous hypoxic pressor reactivity of blood-perfused lungs, but it reversed the blunted pressor reactivity of lungs perfused with blood collected from adrenalectomized rats. The potentiation of hypoxic vasoconstriction by dexamethasone required greater than 40 min to develop and was inhibited by a 100-fold higher concentration of progesterone, a glucocorticoid receptor antagonist. Although dexamethasone and the cyclooxygenase blocker meclofenamate (3.1 X 10(-5) M) caused similar decreases in perfusate levels of cyclooxygenase metabolites, the glucocorticoid was much more effective in inducing hypoxic vasoconstriction in PSS-perfused lungs. Thus a reduction of cyclooxygenase metabolism might have contributed to, but did not fully account for, the glucocorticoid effect. Dexamethasone also caused small increases in base-line perfusion pressure and in pressor reactivity to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
D000315:Adrenalectomy; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology; D007773:Lactates / Q000097:blood; D010477:Perfusion; D011374:Progesterone / Q000494:pharmacology; D011453:Prostaglandins / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects*; D011773:Pyruvates / Q000097:blood; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D007773:Lactates; D011453:Prostaglandins; D011773:Pyruvates; D000804:Angiotensin II; D012965:Sodium Chloride; D011374:Progesterone; D003907:Dexamethasone