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NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide.
Am J Physiol Heart Circ Physiol. 2001 Dec; 281(6):H2328-36.AJ

Abstract

The paraventricular nucleus (PVN) of the hypothalamus is an important site of integration in the central nervous system for sympathetic outflow. Both glutamate and nitric oxide (NO) play an important role in the regulation of sympathetic nerve activity. The purpose of the present study was to examine the interaction of NO and glutamate within the PVN in the regulation of renal sympathetic nerve activity in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) were measured in response to administration of N-methyl-D-aspartic acid (NMDA) and N(G)-monomethyl-L-arginine (L-NMMA) into the PVN. We found that microinjection of NMDA (25, 50, and 100 pmol) into the PVN increased RSND, BP, and HR in a dose-dependent manner, reaching 53 +/- 9%, 19 +/- 3 mmHg, and 32 +/- 12 beats/min, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA. On the other hand, inhibition of NO within the PVN by microinjection of L-NMMA also induced increases in RSND, BP, and HR in a dose-dependent manner, reaching 48 +/- 6.5%, 11 +/- 4 mmHg, and 55 +/- 16 beats/min, respectively, at the highest dose. This sympathoexcitatory response was eliminated by prior microinjection of DL-2-amino-5-phosphonovaleric acid, an antagonist of the NMDA receptor. Furthermore, with the use of the push-pull technique, perfusion of glutamate (0.5 micromol) or NMDA (0.1 nmol) into the PVN induced an increase in NO release. In conclusion, our data indicate that NMDA receptors within the PVN mediate an excitatory effect on renal sympathetic nerve activity, arterial BP, and HR. NO in the PVN, which is released by activation of the NMDA receptor, also inhibits NMDA-mediated increases in sympathetic nerve activity. This negative feedback of NO on the glutamate system within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow in normal and pathophysiological conditions known to have increased sympathetic tone.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, 68198-4547, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11709399

Citation

Li, Y F., et al. "NMDA-mediated Increase in Renal Sympathetic Nerve Discharge Within the PVN: Role of Nitric Oxide." American Journal of Physiology. Heart and Circulatory Physiology, vol. 281, no. 6, 2001, pp. H2328-36.
Li YF, Mayhan WG, Patel KP. NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide. Am J Physiol Heart Circ Physiol. 2001;281(6):H2328-36.
Li, Y. F., Mayhan, W. G., & Patel, K. P. (2001). NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide. American Journal of Physiology. Heart and Circulatory Physiology, 281(6), H2328-36.
Li YF, Mayhan WG, Patel KP. NMDA-mediated Increase in Renal Sympathetic Nerve Discharge Within the PVN: Role of Nitric Oxide. Am J Physiol Heart Circ Physiol. 2001;281(6):H2328-36. PubMed PMID: 11709399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA-mediated increase in renal sympathetic nerve discharge within the PVN: role of nitric oxide. AU - Li,Y F, AU - Mayhan,W G, AU - Patel,K P, PY - 2001/11/16/pubmed PY - 2002/1/10/medline PY - 2001/11/16/entrez SP - H2328 EP - 36 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 281 IS - 6 N2 - The paraventricular nucleus (PVN) of the hypothalamus is an important site of integration in the central nervous system for sympathetic outflow. Both glutamate and nitric oxide (NO) play an important role in the regulation of sympathetic nerve activity. The purpose of the present study was to examine the interaction of NO and glutamate within the PVN in the regulation of renal sympathetic nerve activity in rats. Renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) were measured in response to administration of N-methyl-D-aspartic acid (NMDA) and N(G)-monomethyl-L-arginine (L-NMMA) into the PVN. We found that microinjection of NMDA (25, 50, and 100 pmol) into the PVN increased RSND, BP, and HR in a dose-dependent manner, reaching 53 +/- 9%, 19 +/- 3 mmHg, and 32 +/- 12 beats/min, respectively, at the highest dose. These responses were significantly enhanced by prior microinjection of L-NMMA. On the other hand, inhibition of NO within the PVN by microinjection of L-NMMA also induced increases in RSND, BP, and HR in a dose-dependent manner, reaching 48 +/- 6.5%, 11 +/- 4 mmHg, and 55 +/- 16 beats/min, respectively, at the highest dose. This sympathoexcitatory response was eliminated by prior microinjection of DL-2-amino-5-phosphonovaleric acid, an antagonist of the NMDA receptor. Furthermore, with the use of the push-pull technique, perfusion of glutamate (0.5 micromol) or NMDA (0.1 nmol) into the PVN induced an increase in NO release. In conclusion, our data indicate that NMDA receptors within the PVN mediate an excitatory effect on renal sympathetic nerve activity, arterial BP, and HR. NO in the PVN, which is released by activation of the NMDA receptor, also inhibits NMDA-mediated increases in sympathetic nerve activity. This negative feedback of NO on the glutamate system within the PVN may play an important role in maintaining the overall balance and tone of sympathetic outflow in normal and pathophysiological conditions known to have increased sympathetic tone. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/11709399/NMDA_mediated_increase_in_renal_sympathetic_nerve_discharge_within_the_PVN:_role_of_nitric_oxide_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.2001.281.6.H2328?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -