Down-regulation of chemokine Ccl5 gene expression in the NTS of SHR may be pro-hypertensive

Objectives Recent studies have demonstrated that proinflammatory molecules such as junctional adhesion molecules-1 are highly expressed in the nucleus tractus solitarii (NTS) of the spontaneously hypertensive rat (SHR), compared to normotensive rats (Wistar-Kyoto rats: WKY), suggesting that the NTS of SHR may exhibit an abnormal inflammatory state. In the present study, we tested whether gene expression of inflammatory markers such as cytokines and chemokines is altered in the NTS of SHR and whether this contributes to the hypertensive phenotype in the SHR. Methods We have performed RT2 Profiler PCR arrays in the NTS of SHR and WKY, which were designed to specifically target major cytokines/chemokines and their receptors. To validate PCR array results quantitative RT-PCR was performed. Microinjection studies using anesthetized rats were also carried out to examine whether validated inflammatory molecules exhibit functional roles on cardiovascular regulation at the level of the NTS. Results Five inter-related transcripts were identified to be differentially expressed between the NTS of SHR and WKY. They include chemokine (C-C motif) ligand 5 (Ccl5), and its receptors, chemokine (C-C motif) receptor 1 and 3. All of them were down-regulated in the NTS of SHR compared to WKY. Moreover, we found that the protein Ccl5 microinjected into the NTS significantly decreased baseline arterial pressure and that the response was greater in the SHR compared to the WKY (-33.2 +/- 3.2 vs. -8.8 +/- 1.6mmHg, P < 0.001), demonstrating that its downregulation in the NTS may contribute to hypertension in the SHR. Conclusion We suggest that gene expression of specific chemokines may be down-regulated to protect further inflammatory reactions in the NTS of SHR at the expense of arterial hypertension. J Hypertens 29:732-740 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.