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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on May 18, 2005; DOI: 10.1124/jpet.105.087510


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Received for publication April 6, 2005.
Revised May 9, 2005.
Accepted for publication May 10, 2005.

MAPK PHOSPHORYLATION IN THE ROSTRAL VENTROLATERAL MEDULLA PLAYS A KEY ROLE IN IMIDAZOLINE (I1) RECEPTOR MEDIATED HYPOTENSION

Jian Zhang 1 Abdel A. Abdel-Rahman 2*

1 East Carolina University 2 East Carolina University School of Medicine

* Address correspondence to: E-mail: abdelrahmana{at}mail.ecu.edu

Abstract

Our previous study showed that rilmenidine, a selective I1-imidazoline receptor agonist, enhanced the phosphorylation of mitogen-activated protein kinase (MAPKp42/44,) via the phosphatidylcholine-specific phospholipase C (PC-PLC) pathway in pheochromocytoma cell line (PC12). In the present study we tested the hypothesis that enhancement of MAPK phosphorylation in the rostral ventrolateral medulla (RVLM) contributes to the hypotensive response elicited by I1 receptor activation in vivo. Systemic rilmenidine (600 µg/kg, i.v.) elicited hypotension and bradycardia along with significant elevation in MAPKp42/44, detected by immunohistochemistry, in RVLM neurons. To obtain conclusive evidence that the latter response was I1-receptor mediated, similar hypotensive responses were elicited by intracisternal (i.c.) rilmenidine (25 µg/rat) or the highly selective {alpha}2-agonist {alpha}-methylnorepinephrine ({alpha}-MNE, 4 µg/rat). An increase in RVLM MAPKp42/44 occurred only following rilmenidine. Further, pretreatment with efaroxan (0.15 µg/rat, i.c.), a selective I1-imidazoline receptor antagonist, or with PD 98059 (5 µg/rat, i.c.), a selective ERK1/2 inhibitor, significantly attenuated the hypotensive response and the elevation in RVLM MAPKp42/44 elicited by i.c. rilmenidine. The findings suggest that MAPK phosphorylation in the RVLM contributes to the hypotensive response induced by I1 receptor activation and presents in vivo evidence that distinguishes the neuronal responses triggered by the I1-receptor from those triggered by the {alpha}2-adrenergic receptor.


Key words: Hypertension, arterial, Mitogen-activated protein kinase (MAPK), Receptors, adrenergic alpha, Receptors, imidazoline, Rilmenidine, Rostral ventrolateral medulla (RVLM)


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