Brain chemokine stromal cell‐derived factor‐1/CXCL12 modulates cardiovascular function and sympathetic drive in sham‐operated and heart failure rats

Abstract

Chemokines play a critical role in coordinating inflammatory and immune responses. In the brain, chemokines and their receptors are predominantly expressed in the cardiovascular and autonomic regions, including the paraventricular nucleus (PVN) of hypothalamus, the subfornical organ (SFO) and the supraoptic nucleus (SON). Chemokine stromal cell‐derived factor‐1 (SDF‐1)/CXCL12 has been reported to modulate arginine vasopressin release via its CXCR4 receptor in PVN and SON. This study investigated a potential role for brain chemokine SDF‐1 and CXCR4 in regulating blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in sham‐operated (SHAM) and heart failure (HF) rats. Adult male Sprague Dawley rats were studied 4–5 weeks after coronary artery ligation to induce HF, or sham ligation. Confocal images revealed more intense SDF‐1 expression in PVN and SFO of HF than SHAM rats. Intracerebroventricular injection of recombinant SDF‐1 significantly (p<0.05) decreased BP, HR and RSNA in both SHAM and HF rats. Blockade of CXCR4 with a blocking peptide or a selective antagonist AMD3100 markedly (p<0.01) increased BP, HR and RSNA in SHAM and HF rats. These data suggest that brain chemokine SDF‐1 and its receptor play an important role in regulating cardiovascular function and sympathetic drive in normal and pathophysiological conditions. Supported by a VA Merit Review Award and NIH RO1 HL073986.