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CENTRAL NERVOUS SYSTEM

Aminopropionic Acid Receptors in Paraventricular Nucleus Mediate Pressor and Vasopressin Responses to Endothelin-1 in Subfornical Organ

Departments of Medicine and Physiology, Wayne State University School of Medicine and John D. Dingell VA Medical Center, Detroit, Michigan 48201

To whom requests for reprints should be addressed at ¹ Departments of Medicine and Physiology, Wayne State University School of Medicine, 4160 John R Street, #908, Detroit, MI 48201. E-mail: nrossi{at}med.wayne.edu

Abstract

Endothelin-1 (ET-1) acts at selected brain loci to elicit a pressor response and secretion of vasopressin (AVP). Glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype mediate ET-1–induced AVP secretion in vitro, but the role of glutamatergic receptors in the pressor response and the secretion of AVP in vivo has not been studied. We hypothesized that both the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) would be suppressed by ionotropic glutamatergic receptor antagonists in the paraventricular nucleus (PVN). Sinoaortic denervated male Long Evans rats were equipped with intracerebral cannulae directed into the SFO and the magnocellular region of the PVN bilaterally. Experiments were performed 5 days later in conscious rats. Direct injection of 5 pmol ET-1 into the SFO resulted in a 20 ± 3 mm Hg increase in mean arterial pressure (MAP) (± SE) and a 14.1 ± 0.3 pg/ml increase in the mean plasma AVP level (± SE) (P < 0.001 vs. artificial CSF) that was blocked by selective ET_A inhibition. Neither the pressor response nor the increase in plasma AVP in response to ET-1 was altered despite prior injection of the NMDA blocker diclozipine (5 µg, MK801) into PVN bilaterally. In contrast, bilateral PVN injection with 6-cyano-7-nitroquinoxaline-2,3-dione (40 nmol, CNQX) prevented the pressor response (MAP ± SE, – 4 ± 4 mm Hg) and also inhibited AVP secretion (mean AVP level ± SE, 0.16 ± 0.50 pg/ ml) (P < 0.001 vs. vehicle in PVN after injection of ET-1 into SFO). These findings support the conclusion that both the pressor response and AVP secretion in response to ET-1 acting at the SFO are mediated by a non-NMDA, most likely an aminopropionic acid glutamatergic receptor within the PVN.

Key Words: AMPA receptors • endothelin • glutamatergic receptors • Long Evans rats • NMDA receptors • paraventricular nucleus • posterior pituitary • subfornical organ • vasopressin