Inhibition of hypoxia-induced ADH release by meclofenamate in the conscious dog.
Release of antidiuretic hormone (ADH) due to hypoxic stimuli has been documented in several in vivo models. The current study was performed to determine whether 1) hypoxia causes ADH release in the conscious normovolemic dog and 2) whether endogenous prostaglandins are involved in hypoxic ADH release. Five conscious dogs were made hypoxic by inhalation of 10% O2. Dogs were studied both with and without pretreatment with meclofenamate (2 mg/kg iv and 2 mg . kg-1 . h-1). Hypoxic exposure resulted in elevated plasma ADH; however, meclofenamate totally blocked this response. Hemodynamic responses to hypoxia were unaffected by meclofenamate. In addition, plasma osmolality was unchanged by hypoxia in both groups. Since meclofenamate does not cross the blood-brain barrier, it is concluded that the release of ADH by hypoxia in the conscious dog may be mediated by endogenous prostaglandins produced outside the central nervous system. It appears that elevated renal prostaglandin release, increased ADH, and hemodynamic alterations could all interact to determine the final renal response to hypoxia.
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D003243:Consciousness; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D008469:Meclofenamic Acid / Q000494:pharmacology*; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000097:blood; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D062367:ortho-Aminobenzoates; D014667:Vasopressins; D008469:Meclofenamic Acid