Unique levels of expression of N-methyl-D-asparatate receptor subunits and neuronal nitric oxide synthase in the rostral ventrolateral medulla of the spontaneously hypertensive rat

M.A. Edwards, R.A. Loxley, K. Powers-Martin, J. Lipski, Doug Mckitrick, Leonard Arnolda, J.K. Phillips

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    The rostral ventrolateral medulla (RVLM) is the major brainstem region contributing to sympathetic control of blood pressure. We havecompared the expression of N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A–D), NR1 splice variants (NR1-1a/1b, -2a/2b, -3a/3b, -4a/4b), and the neuronal and inducible isoforms of NO synthase (nNOS and iNOS) in the RVLM of Wistar Kyoto (WKY) andspontaneously hypertensive rats (SHR), based on the hypothesis that altered NMDA receptor make-up or altered expression of endogenousNO may be associated with the increase in sympathetic output described from this site in hypertension. Total RNAwas extracted and reversetranscribed from the RVLM of mature male WKY and SHR (16–23 weeks). Conventional polymerase chain reaction (PCR) indicated thatonly the NR1 splice variants NR1-2a, NR1-2b, NR1-4a and NR1-4b were expressed in the RVLM of either species. Quantitative real-timePCR indicated that for both strains of rat, mRNA for the NR1 subunit (all splice variants) was the most abundant (16.5-fold greater, P V 0.05,relative to the NR2A subunit). Amongst the NR2A–D subunits, NR2C was the most abundant (7- and 1.7-fold greater relative to the NR2Asubunit, P V 0.05, WKYand SHR, respectively). Relative to WKY, mRNA levels for the NR2C and NR2D subunits in the SHR RVLM weresignificantly lower (0.3- and 0.25-fold less, P V 0.05), while nNOS was significantly higher (1.76-fold greater, P V 0.05). This was confirmedimmunohistochemically for nNOS expression. These results demonstrate differential expression levels of NMDA receptor subunits and NOSisoforms in the RVLM region of SHR when compared to WKY rats.D 2004 Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)33-43
    JournalMolecular Brain Research
    Volume129
    Issue number1/2
    DOIs
    Publication statusPublished - 2004

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