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Pro‐hypertensive role for leukotriene B4 receptors in the spontaneously hypertensive rat
Author(s) -
Hendy Emma Bernice,
Waki Hidefumi,
Paton Julian F. R.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.968.6
Subject(s) - leukotriene b4 , receptor , medicine , spontaneously hypertensive rat , blood pressure , vasomotor , endocrinology , inflammation , leukotriene receptor , leukotriene , pharmacology , antagonist , asthma
cDNA microarray analysis of the nucleus tractus solitarii (NTS) has indicated leukotriene B4 12‐hydroxydehydrogenase (LTB4 12‐HD) is down regulated in the spontaneous hypertensive rat (SHR) compared to its normotensive control (Wistar‐Kyoto or WKY; Waki et al. 2004; J.Physiol. 560P, PC6). As LTB4 12‐HD breaks down LTB4, we propose that it is up regulated in the NTS of the SHR, promoting vascular inflammation. To investigate the role of LTB4 receptors in the maintenance of the hypertension in the SHR, we have assessed whether systemic antagonism of LTB4 receptors has an anti‐hypertensive effect. In radio‐telemetered SHR, chronic oral administration of a LTB4 inhibitor (CP‐105696) was given in their drinking water (1 mg/ml in 1.25% DMSO). In all cases, a significant hypotensive effect of −13.2 ± 1.4 mmHg (P<0.05, n=5) was seen 11 ± 1.6 days after administration. In contrast, inhibiting LTB4 receptors in WKY rats was ineffective (n=5). When vehicle (1.25% DMSO) alone was added to drinking water there was no change in arterial pressure (n=2). These data indicate that LTB4 receptor activation contributes to the hypertension in the SHR. Our finding is consistent with the notion that the hypertension in the SHR is dependent, in part, on inflammation of the vasculature, which may include that within NTS and other brain regions controlling vasomotor tone. British Heart Foundation funded research.