CCL5 Inhibits Elevation of Blood Pressure and Expression of Hypertensive Mediators in Developing Hypertension State Spontaneously Hypertensive Rats

Abstract

CCL5, a proinflammatory chemokine, has been shown to attenuate angiotensin (Ang) II-induced expression of hypertensive mediators as well as Ang II-induced inhibition of anti-hypertensive mediator expression in vascular smooth muscle cells (VSMCs) of spontaneously hypertensive rats (SHR). In the present study, functional roles of CCL5 on hypertension were examined in developing hypertension state SHR (DHSHR). DHSHR at an age of 8 weeks were injected CCL5 (1.5 μg/kg) subcutaneously twice a day for 3 weeks (SHRi, n=5). Control groups consisted of normal age-matched saline-treated SHR (SHRc, n=5) and normotensive Wistar-Kyoto rats (WKY, n=5). Effect of CCL5 on blood pressure was measured before treatment, weekly during treatment, and 1 day after the final injection. After injecting for 3 weeks, effects of CCL5 on expression of hypertensive mediators were examined in thoracic aorta tissues and VSMCs. Blood pressure in SHRi was maintained without any elevation during the treatment period, whereas blood pressure in SHRc progressively increased with age. Expression of Ang II subtype I receptor was reduced in SHRi thoracic aorta tissues and VSMCs compared to those in SHRc. In addition, expression levels of hypertensive mediators were significantly reduced in SHRi thoracic aorta tissues and VSMCs compared to those in SHRc. In contrast, AMP-activated protein kinase (AMPK) activity and interleukin-10 (IL-10) expression were elevated in SHRi thoracic aorta tissues and VSMCs compared to levels in SHRc. These results suggest that reduction of hypertensive mediators and elevation of antihypertensive mediators by CCL5 treatment promotes maintenance of blood pressure in DHSHR.

Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion

“…Meanwhile, a recent study showing that melatonin could reduce MCP-1 expression suggested that agomelatine may share this effect, which the present study has determine to be correct [ 53 ]. CCL5 may act as a regulatory factor against Ang II-induced hypertension [ 54 ], but has also been recognized as an indicator of short-term mortality in patients with CVD [ 55 ]. The inhibitory role of agomelatine on these chemokines indicates that it could alleviate the recruitment of immune cells to the surface of endothelial cells.…”