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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Hypertension 2013 ; 61 (1): 194-201 Nephropedia Template TP
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EXCESSIVE LEUKOTRIENE B4 IN NUCLEUS TRACTUS SOLITARII IS PROHYPERTENSIVE IN SPONTANEOUSLY HYPERTENSIVE RATS #MMPMID23172924
Hypertension 2013[Jan]; 61 (1): 194-201 PMID23172924show ga
Inflammation within the brainstem microvasculature has been associated with chronic cardiovascular diseases. We found that the expression of several enzymes involved in arachidonic acid (AA) - leukotriene B4 (LTB4) production was altered in NTS of SHR. LTB4 produced from AA by 5-lipoxygenase (5LOX) is a potent chemoattractant of leukocytes. Leukotriene B4-12-hydroxydehydrogenase (LTB4-12-HD), which degrades leukotriene B4 (LTB4), was down-regulated compared to Wistar-Kyoto rats (WKY). Quantitative RT-PCR revealed that LTB4-12-HD was reduced by 63 and 58% in the NTS of adult SHR and pre-hypertensive (PH) SHR respectively, compared to age-matched WKY rats (n=6). 5LOX gene expression was up-regulated in the NTS of SHR (~50%; n=6). LTB4 levels were increased in the NTS of the SHR (17%; n=10, p<0.05). LTB4 receptors BLT1 (but not BLT2), were expressed on astroglia in the NTS but not neurons or vessels. Microinjection of LTB4 into the NTS of WKY rats increased both leukocyte adherence and arterial pressure for over 4 days (peak: +15 mmHg; P<0.01). In contrast, blockade of NTS BLT1 receptors lowered blood pressure in the SHR (peak: -13 mmHg; P<0.05) but not WKY rats. Thus, excessive amounts of LTB4 in NTS of SHR possibly as a result of up-regulation of 5LOX and down regulation of LTB412-HD, can induce inflammation. Since blockade of NTS BLT1 receptors lowered arterial pressure in the SHR their endogenous activity may contribute to the hypertensive state of this rodent model. Thus, inflammatory reactions in the brainstem are causally associated with neurogenic hypertension.