Activation of the
neurokinin 3 receptor (NK3R) by a receptor agonist,
hypotension, and hyperosmolarity results in the internalization of NK3R expressed by magnocellular neurons and the release of
vasopressin (VP) and
oxytocin (OT) into the circulation. The contribution of NK3R activation to the release of VP and OT in response to hyperosmolarity and
hypotension was evaluated by measuring the release of both
hormones following pretreatment with a selective NK3R antagonist,
SB-222200. Freely behaving male rats were given an
intraventricular injection of either 0.15 M NaCl or 250, 500, or 1,000 pmol
SB-222200, and then were administered an
intravenous infusion of 2 M NaCl or 0.15 M NaCl (experiment 1), or a bolus intra injection of 0.15 M NaCl or
hydralazine (HDZ), a
hypotension-inducing
drug (experiment 2). Blood samples were taken from indwelling arterial
catheters at various time points for 1-2 h, both before and
after treatments. Plasma VP and OT levels were determined by ELISA. Blockade of NK3R did not affect the baseline levels of either
hormone. In contrast, pretreatment with
SB-222200 significantly reduced ( approximately 60%) or abolished the release of VP and OT, respectively, to 2 M NaCl infusion. HDZ-induced VP and OT release was eliminated by pretreatment with 500 pmol
SB-222200. Therefore, NK3R activation contributes significantly to the systemic release of both VP and OT in response to osmotic and hypotensive challenges.