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Effects of Chemokines SDF‐1/CXCL12 and Fractalkine/CX3CL1 on Cardiovascular Function and Sympathetic Drive in SHR Rats

The expression of chemokines and their receptors throughout the brain, with a predominant localization in cardiovascular and autonomic regions such as the paraventricular nucleus (PVN) of hypothalamus, the supraoptic nucleus, and the subfornical organ (SFO), suggests that they play a role in the regulation of cardiovascular function and sympathetic nerve activity. Our previous work has demonstrated that the chemokines stromal cell‐derived factor‐1 (SDF‐1) and fractalkine regulate blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in sham‐operated and heart failure rats. The present study examined the potential role of SDF‐1 and fractalkine in regulating sympathetic and hemodynamic responses in WKY and SHR rats. Confocal immunofluorescent images revealed that SDF‐1 and fractalkine expression was significantly increased in the PVN and SFO of SHR compared with WKY rats. In urethane anesthetized adult (12–14 weeks) male rats, intracerebroventricularly administered SDF‐1 (25 ng) and fractalkine (25 ng) induced substantial increases (p<0.05) in BP, HR and RSNA in SHR but not WKY. These data demonstrate that brain chemokines such as SDF‐1 and fractalkine can regulate cardiovascular function and sympathetic drive, and so may contribute to the development of hypertension in SHR rats. Supported by a VA Merit Review Award and NIH RO1 HL073986.