Nitric oxide-cGMP-PKG signaling in the bed nucleus of the stria terminalis modulates the cardiovascular responses to stress in male rats.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9111390 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7862 (Electronic) Linking ISSN: 0924977X NLM ISO Abbreviation: Eur Neuropsychopharmacol Subsets: MEDLINE

Original Publication: Amsterdam : Elsevier, c1990-

Cardiovascular System/*metabolism ; Cyclic GMP/*metabolism ; Cyclic GMP-Dependent Protein Kinases/*metabolism ; Nitric Oxide/*metabolism ; Septal Nuclei/*metabolism ; Stress, Psychological/*metabolism; Animals ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Cardiovascular System/drug effects ; Cyclic GMP/antagonists & inhibitors ; Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors ; Heart Rate/drug effects ; Heart Rate/physiology ; Male ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Rats, Wistar ; Restraint, Physical/physiology ; Restraint, Physical/psychology ; Septal Nuclei/drug effects ; Skin Temperature/drug effects ; Skin Temperature/physiology ; Tachycardia/metabolism

The bed nucleus of the stria terminalis (BNST) constitutes an important component of neural substrates of physiological and behavioral responses to aversive stimuli, and it has been implicated on cardiovascular responses evoked by stress. Nevertheless, the local neurochemical mechanisms involved in BNST control of cardiovascular responses during aversive threats are still poorly understood. Thus, the aim of the present study was to assess the involvement of activation in the BNST of the neuronal isoform of the enzyme nitric oxide synthase (nNOS), as well as of signaling mechanisms related to nitric oxide effects such as soluble guanylate cyclase (sGC) and protein kinase G (PKG) on cardiovascular responses induced by an acute session of restraint stress in male rats. We observed that bilateral microinjection of either the nonselective NOS inhibitor Nω-Nitro-L-arginine methyl ester (L-NAME), the selective nNOS inhibitor Nω-Propyl-L-arginine (NPLA) or the sGC inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) into the BNST enhanced the tachycardic response and decreased the drop in tail cutaneous temperature evoked by acute restraint stress, but without affecting the increase on blood pressure. Bilateral BNST treatment with the selective PKG inhibitor KT5823 also facilitated the heart rate increase and decreased the drop in cutaneous temperature, in addition to enhancing the blood pressure increase. Taken together, these results provide evidence that NO released from nNOS and activation of sGC and PKG within the BNST play an inhibitory influence on tachycardia to stress, whereas this signaling mechanism mediates the sympathetic-mediated cutaneous vasoconstriction.
(Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Keywords: BNST; Blood pressure; Guanylate cyclase; Heart rate; Stress; Sympathetic

31C4KY9ESH (Nitric Oxide)
EC 1.14.13.39 (Nitric Oxide Synthase)
EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
H2D2X058MU (Cyclic GMP)

Date Created: 20171125 Date Completed: 20181211 Latest Revision: 20181211

20240829

10.1016/j.euroneuro.2017.11.015

29169825