J Bacteriol Virol.  2015 Jun;45(2):138-150. 10.4167/jbv.2015.45.2.138.

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

• Kim HY
• Cha HJ
• Choi JH
• Kang YJ
• Park SY
• Kim HS

• KMID: 2149214
• DOI: http://doi.org/10.4167/jbv.2015.45.2.138

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 microg/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 anti-hypertensive mediators by CCL5 treatment promotes maintenance of blood pressure in DHSHR.

Keyword

CCL5; Hypertensive mediator; Vascular smooth muscle cells; Blood pressure

MeSH Terms

AMP-Activated Protein Kinases
Angiotensins
Animals
Aorta, Thoracic
Blood Pressure*
Hypertension*
Interleukin-10
Muscle, Smooth, Vascular
Rats
Rats, Inbred SHR*
AMP-Activated Protein Kinases
Angiotensins
Interleukin-10