Published Online
on April 9, 2007

A more recent version of this article appeared on June 1, 2007

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Submitted on December 5, 2006
Revised on December 12, 2006

Junctional Adhesion Molecule-1 Is Upregulated in Spontaneously Hypertensive Rats. Evidence for a Prohypertensive Role Within the Brain Stem

Hidefumi Waki^*; Beihui Liu; Masao Miyake; Kiyoaki Katahira; David Murphy; Sergey Kasparov; and Julian F.R. Paton

From the Department of Physiology, Bristol Heart Institute, School of Medical Sciences (H.W., B.L., S.K., J.F.R.P.), and Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology (D.M.), University of Bristol, Bristol, United Kingdom; and the Department of Physiology (M.M.) and Experimental Animal Center (K.K.), Fukushima Medical University School of Medicine, Fukushima, Japan

^* To whom correspondence should be addressed. E-mail: h-waki{at}wakayama-med.ac.jp.

Abstract--Junctional adhesion molecule-1 (JAM-1) forms part of the tight junction between adjacent endothelial cells. Using microarray technology, we showed previously that JAM-1 was differentially expressed in the brain stem of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto (WKY) rats. In this study, we quantified the expression of JAM-1 in the brain stem of spontaneously hypertensive rats and WKY rats and established whether any differential expression was confined to this region of the brain or was ubiquitous throughout the central nervous system and, indeed, the whole body. Because the nucleus tractus solitarii plays a pivotal role in arterial pressure regulation, we assessed whether JAM-1 in this region affects the chronic regulation of arterial pressure. Real time RT-PCR revealed that JAM-1 mRNA was upregulated in multiple regions of the brain and all of the peripheral vascular beds studied. In the nucleus tractus solitarii, the level of JAM-1 mRNA was significantly higher in both young (3-week-old, prehypertensive) and adult male spontaneously hypertensive rats (15 to 18 weeks old) than that of age-matched WKY rats (fold differences; prehypertensives: 1.01±0.06 versus 1.59±0.13; n=10; P<0.01; adult: 1.08±0.14 versus 2.86±0.57; n=10; P<0.01). After adenoviral-mediated expression of JAM-1 in the nucleus tractus solitarii of adult WKY rats (15 weeks old; n=6), systolic pressure was increased from 120±4 to 132±4 mm Hg (P<0.01). Our data suggest that JAM-1 expression in the spontaneously hypertensive rat is upregulated throughout the body compared with the WKY rat and that this is not secondary to the hypertension. When JAM-1 is expressed in the nucleus tractus solitarii, it raises arterial pressure, suggesting a novel prohypertensive role for this protein within the brain stem.

Key words: hypertension • brain stem • inflammation • baroreflex control • adhesion molecules

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