Reparixin, an Inhibitor of CXCR1 and CXCR2 Receptor Activation, Attenuates Blood Pressure and Hypertension-Related Mediators Expression in Spontaneously Hypertensive Rats

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Reparixin, an inhibitor of CXCL8 receptor CXCR1 and CXCR2 activation, has been shown to attenuate inflammatory responses in various injury models. In the present study, the hypertension-related functional roles of reparixin were examined in hypertensive animals. Spontaneously hypertensive rats (SHR) at the age of 18 weeks were administered a subcutaneous injection of reparixin (5 mg/kg) daily for 3 weeks (SHR-R, n=5). Control groups consisted of normal saline-treated SHR (SHR-N, n=5) and normotensive Wistar–Kyoto rats (WKY-N, n=5). Reparixin effectively decreased systolic blood pressure and increased the blood flow. The thoracic aorta wall thickness was significantly decreased in SHR-R compared to SHR-N. Expressions of CXCL8, CCL2, 12-lipoxygenase (LO) and endothelin (ET)-1 were significantly decreased in SHR-R thoracic aorta tissues compared to SHR-N. Furthermore, expression of angiotensin II subtype I receptor (AT1R) protein was decreased in SHR-R thoracic aorta tissues compared to SHR-N. In addition, the plasma levels of nitric oxide were slightly elevated in SHR-R compared to the levels in SHR-N. These findings indicate that inhibition of hypertension-related mediators by reparixin results in the reduction of blood pressure in SHR. Therefore, these results suggest that reparixin-mediated blockade of CXCL8 receptor activation attenuates vascular hypertension in SHR.