Pressor effect of apelin-13 in the rostral ventrolateral medulla

Role of NAD(P)H oxidase-derived superoxide

Fanrong Yao, Amit Modgil, Qi Zhang, Ajeeth Pingili, Neha Singh, Stephen T. O'Rourke, Chengwen Sun

Research output: Contribution to journalArticle

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Abstract

Microinjection of apelin-13 into the rostral ventrolateral medulla (RVLM) in the brainstem increases blood pressure in rats. In the present study, we tested the hypotheses that apelin-13 directly stimulates neuronal activity in neurons cultured from the brainstem and that NAD(P)H oxidase-derived reactive oxygen species are involved in this action of apelin-13. Microinjection of apelin-13 into the RVLM resulted in increases in arterial pressure and in renal sympathetic nerve activity in Sprague-Dawley rats. The pressor effect of apelin-13 was attenuated by the specific NAD(P)H-oxidase inhibitor gp91ds-tat. In neurons cultured from the ventral brainstem, spontaneous action potentials were recorded using current-clamp recording. Superfusion of neurons with apelin-13 (100 nM) increased the neuronal firing rate from 0.79 ± 0.14 to 1.45 ± 0.26 Hz (n = 7, P < 0.01) in angiotensin II receptor-like 1-positive neurons, identified with single-cell reverse transcriptase-polymerase chain reaction. Neither the angiotensin II type 1 receptor antagonist losartan nor the angiotensin II type 2 receptor antagonist 1-[[4-(dimethylamino)-3- methylphenyl[methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c] pyridine-6-carboxylic acid ditrifluoroacetate (PD123319) altered the positive chronotropic effect of apelin-13. Pretreatment of cells with either the reactive oxygen species scavenger superoxide dismutase [polyethylene glycol-superoxide dismutase (PEG-SOD), 25 U/ml] or with gp91ds-tat significantly attenuated the chronotropic action of apelin-13. PEG-SOD and gp91ds-tat alone had no effect on basal neuronal firing. In addition, apelin-13 significantly increased NAD(P)H oxidase activity and elevated intracellular superoxide levels in neuronal cultures. The superoxide generator xanthine-xanthine oxidase also increased neuronal activity in neurons, mimicking the neuronal response to apelin-13. These observations provide the first evidence that apelin-13 directly increases neuronal activity via stimulation of NAD(P)H oxidasederived superoxide, a cellular signaling mechanism that may be involved in the pressor effect of apelin-13 in the RVLM.

Original languageEnglish (US)
Pages (from-to)372-380
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume336
Issue number2
DOIs
StatePublished - Feb 1 2011

Fingerprint

NADPH Oxidase
Superoxides
Neurons
Brain Stem
Microinjections
apelin-13 peptide
Reactive Oxygen Species
Angiotensin II Type 2 Receptor Blockers
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptors
Xanthine
Losartan
Xanthine Oxidase
Reverse Transcriptase Polymerase Chain Reaction
NAD
Action Potentials
Superoxide Dismutase
Sprague Dawley Rats
Arterial Pressure

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Molecular Medicine

Cite this

Pressor effect of apelin-13 in the rostral ventrolateral medulla : Role of NAD(P)H oxidase-derived superoxide. / Yao, Fanrong; Modgil, Amit; Zhang, Qi; Pingili, Ajeeth; Singh, Neha; O'Rourke, Stephen T.; Sun, Chengwen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 336, No. 2, 01.02.2011, p. 372-380.

Research output: Contribution to journalArticle

Yao, Fanrong ; Modgil, Amit ; Zhang, Qi ; Pingili, Ajeeth ; Singh, Neha ; O'Rourke, Stephen T. ; Sun, Chengwen. / Pressor effect of apelin-13 in the rostral ventrolateral medulla : Role of NAD(P)H oxidase-derived superoxide. In: Journal of Pharmacology and Experimental Therapeutics. 2011 ; Vol. 336, No. 2. pp. 372-380.
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