title: Reparixin, an inhibitor of CXCR1 and CXCR2 receptor activation, attenuates blood pressure and hypertension-related mediators expression in spontaneously hypertensive rats.
abstract: 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 (AT(1)R) 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.
authors.affiliation: Department of Microbiology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Namgu, Daegu 705–717, South Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Choi
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.forename: Hyoung Chul
authors.initials: HC
authors.lastname: Choi
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004334:Drug Administration Schedule; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D044140:Receptor, Angiotensin, Type 1; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D013449:Sulfonamides; D001092:Arachidonate 12-Lipoxygenase; C490707:reparixin