|
|
||||||||
NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION
Department of Cell Biology and Centre for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
Submitted 19 March 2004 ; accepted in final form 31 May 2004
This study was done to investigate the effects of microinjections of adrenomedullin (ADM), a vasoactive neuropeptide, in the rostral ventrolateral medulla (RVLM) on mean arterial pressure (MAP) and heart rate (HR) in urethane-anesthetized rats, and to assess the potential roles of glutamate and nitric oxide (NO) in these effects. Unilateral injections of ADM (0.01 or 0.1 pmol) into the RVLM significantly increased MAP and HR in a dose-dependent manner, whereas ADM at 0.001 pmol was ineffective. Microinjections of ADM (0.01 pmol) outside the RVLM had no effects on MAP or HR. Coinjections of a putative ADM receptor antagonist, ADM2252 (0.01 pmol), abolished the increases in MAP and HR evoked by ADM (0.01 pmol). The vasopressor effects of ADM (0.01 pmol) in the RVLM were abolished by coinjections of either dizocilpine hydrogen maleate (a selective NMDA glutamate receptor antagonist, 500 pmol) or 6-cyano-7-nitroquinoxaline-2,3-dione (a selective non-NMDA glutamate receptor antagonist, 50 pmol). The ADM-induced vasopressor effects were also abolished by coadministration of either 7-nitroindazole sodium salt (a selective neuronal NO synthase inhibitor, 0.05 pmol) or methylene blue (a soluble guanylyl cyclase inhibitor, 100 pmol). These results suggest that ADM in the RVLM stimulates increases in MAP and HR through ADM receptor-mediated mechanisms. These effects are mediated by glutamate via both NMDA and non-NMDA receptors. NO, derived from neuronal NO synthase, also contributes to the ADM-induced vasopressor effects via a soluble guanylyl cyclase-associated signaling pathway.
N-methyl-D-aspartate receptor; non-N-methyl-D-aspartate receptor; neuronal nitric oxide synthase; soluble guanylyl cyclase
This article has been cited by other articles:
![]() |
A. P. Fernandez, J. Serrano, L. Tessarollo, F. Cuttitta, and A. Martinez Lack of adrenomedullin in the mouse brain results in behavioral changes, anxiety, and lower survival under stress conditions PNAS, August 26, 2008; 105(34): 12581 - 12586. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Geambasu and T. L. Krukoff Adrenomedullin acts in the lateral parabrachial nucleus to increase arterial blood pressure through mechanisms mediated by glutamate and nitric oxide Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2008; 295(1): R38 - R44. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Xu and T. L. Krukoff Adrenomedullin Stimulates Nitric Oxide Production from Primary Rat Hypothalamic Neurons: Roles of Calcium and Phosphatases Mol. Pharmacol., July 1, 2007; 72(1): 112 - 120. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |