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This Article Full Text Full Text (PDF) All Versions of this Article: 586/10/2581    most recent jphysiol.2008.150730v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gao, Z. Articles by Li, J. PubMed PubMed Citation Articles by Gao, Z. Articles by Li, J. Related Collections Cardiovascular

¹ Penn State Heart & Vascular Institute, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA

Arachidonic acid and its metabolites produced via cyclooxygenase (COX) and lipoxygenase pathways have been reported to contribute to the cardiovascular reflexes evoked by stimulating thin fibre muscle afferents during muscle contraction. 20-Hydroxyeicosatetraenoic acid (20-HETE), a primarily metabolized product of arachidonic acid by cytochrome P450 enzymes, can be accumulated in contracting muscles. Thus, the purpose of this study was to determine the role of 20-HETE in modulating the reflex sympathetic responses to activation of chemically and mechanically sensitive muscle afferents. The renal sympathetic nerve activity (RSNA) and cardiovascular responses were examined after injections of 20-HETE into the arterial blood supply of the hindlimb muscles of decerebrated rats. This induced a dose-dependent increases in RSNA and mean arterial pressure (MAP). We also tested the hypothesis that 20-HETE would sensitize muscle afferents and, thereby, augment the RSNA and blood pressure response to muscle stretch. The results show that arterial infusion of 20-HETE significantly enhanced the RSNA and MAP responses to muscle stretch. In contrast, N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine, a potent inhibitor of 20-HETE production, attenuated the reflex muscle responses. Furthermore, the sensitizing effect of 20-HETE on the muscle reflex was significantly attenuated after blocking COX activity with indomethacin. Our data suggest that 20-HETE plays a role in modulating muscle afferent-mediated sympathetic responses, probably through engagement of a COX-dependent mechanism.

(Received 4 January 2008; accepted after revision 20 March 2008; first published online 27 March 2008)
Corresponding author J. Li: Heart & Vascular Institute and Department of Medicine, H047, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Email: jzl10{at}psu.edu