title: N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues.
abstract: Excellent reviews on central N-methyl-D-aspartate receptor (NMDAR) signaling and function in cardiovascular regulating neuronal pools have been reported. However, much less attention has been given to NMDAR function in peripheral tissues, particularly the heart and vasculature, although a very recent review discusses such function in the kidney. In this short review, we discuss the NMDAR expression and complexity of its function in cardiovascular tissues. In conscious (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers cardiovascular oxidative stress through the PI3K-ERK1/2-NO signaling pathway, which ultimately leads to elevation in blood pressure. Evidence also implicates Ca release, in the peripheral NMDAR-mediated pressor response. Despite evidence of circulating potent ligands (eg, D-aspartate and L-aspartate, L-homocysteic acid, and quinolinic acid) and also their coagonist (eg, glycine or D-serine), the physiological role of peripheral cardiovascular NMDAR remains elusive. Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become apparent when its signaling is altered by drugs, such as alcohol, which interact with the NMDAR or its downstream signaling mechanisms.
authors.affiliation: *Oak Ridge Institute for Science and Education, Research Triangle Park, NC; and †Department of Pharmacology, Brody School of Medicine, East Carolina University, Greenville, NC.
authors.forename: Marie A
authors.initials: MA
authors.lastname: McGee
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D055808:Drug Discovery / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D011487:Protein Conformation; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D002317:Cardiovascular Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate