C-type natriuretic peptide chronic administration attenuates cardiac fibrosis and inflammation in spontaneously hypertensive rats

PRENTKI, E; CANIFFI, C; BOUCHET, G; GONZÁLEZ MAGLIO, D; TOBLLI, J; COSTA, MA; ARRANZ, C

Conferencia; 7th International Conference on cGMP; 2015

BackgroundGrowing evidence shows that the expression and release of a number ofinflammatory cytokines are increased in hypertension [1,2] and are also presentat sites of cardiovascular fibrosis. In fact, many of these inflammatorymediators are responsible for the activation of collagen producing fibroblasts[3]. In addition, proinflammatory cytokines such as tumor necrosis factor-alpha(TNF-a) and interleukin-1 (IL-1) have shown to stimulate the release of C-typenatriuretic peptide (CNP), indicating a potential role of CNP as a modulator ofthe inflammatory process [4]. The aim of the present study was to evaluate theeffects of chronic CNP treatment on cardiac fibrosis and inflammation inspontaneously hypertensive rats (SHR).Experimental design and methods12-week-old male SHR and Wistar rats were infused through osmotic pumpswith CNP (0,75 μg/hr) or saline (S) for 14 days. Systolic blood pressure (SBP, mmHg) wasrecorded by tail-cuff method. At the end of the treatment, the left ventricle(LV) was extracted to determine left ventricular mass index (LVMI, g LV/mmtibia length), the myocyte area (μm2, Haematoxylin andEosin-stain), fibrosis (% collagen, Picrosirius Red stain) and inflammationparameters (IL-6 and TNF-a, % stain/mm2 by immunohistochemistry, IHC and IL-6,TNF-a and IL-1b, pg/mg protein by ELISA).ResultsTable 1W-S W-CNP SHR-S SHR-CNPSBP 118±2 122±3 175±3* 159±5#LMVI0,023±0,002 0,024±0,001 0,032±0,001* 0,029±0,001Myocyte area 349±11 337±10609±25* 557±35#% Fibrosis 1,54±0,53 1,78±0,17 6,81±0,40* 3,27±0,67#IL-6 (IHC)1,8±1,0 1,3±0,6 19,4±2,7* 2,1±0,7#TNF-a (IHC) 1,1±0,7 1,0±0,5 15,7±3,4*1,5±0,9#IL-6 (ELISA) ? ? 100,1±6,2 81,0±9,0TNF-a (ELISA) ? ? 8,27±0,894,32±0,18#IL-1b (ELISA) ? ? 135,7±5,8 120,3±2,3#Values are means ± SEM.*p