Albuterol-induced erythropoietin production and prostaglandins release in the isolated perfused dog kidney.
The present study was designed to attempt to clarify the mechanism by which the specific beta-2 adrenergic agonist albuterol causes an enhancement of erythropoietin (Ep) production in the isolated perfused dog kidney. We have postulated previously that prostaglandins (PG) release is an early event in initiating a cascade which leads to enhanced kidney production of Ep. In the present study, the posthypoxic dog kidney was perfused for 5 hr with blood containing 500 microgram/l of albuterol. A significant (P<.001) increase in prostaglandin E (PGE) concentration was seen as early as 1 hr and continued to rise over the 5-hr perfusion period. This microgram increase in PGE was correlated with a significant (P<.05) increase in Ep titers in the perfusates after 3 and 5 hr perfusion. The addition of the PG cyclooxygenase inhibitor meclofenamate (1000 micrograms/l) to the perfusate together with albuterol completely abolished the albuterol-induced increase in PGE and Ep generation in the isolated perfused kidney. No significant increase in PGE or Ep titers in the perfusates occurred during the 5-hr perfusion period in the saline and albuterol plus meclofenamate perfused groups. These data suggest that beta-2 adrenergic activation of Ep production is correlated with an increase in PGE production by the kidney which may be related to the mechanism by which beta-2 agonists enhance kidney production of Ep.
D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004921:Erythropoietin / Q000096:biosynthesis*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008469:Meclofenamic Acid / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D004921:Erythropoietin; D008469:Meclofenamic Acid; D000420:Albuterol; D010100:Oxygen