CONICET | Buscador de Institutos y Recursos Humanos

Background and questionThe expression and release of inflammatory cytokinesare increased in hypertension and also present at sites of cardiovascularfibrosis. Such inflammatory mediators are responsible for the activation ofcollagen producing fibroblasts. C-type natriuretic peptide (CNP) release hasbeen shown to be induced by some cytokines such as tumor necrosis factor-alpha(TNF-α) and interleukin-1 (IL-1), suggesting a potentialrole of CNP as a modulator of the inflammatory process. The aim of the presentstudy was to elucidate what effect a chronic CNP administration would have oncardiac fibrosis and inflammation in a genetic model of hypertension (spontaneouslyhypertensive rats, SHR). Experimental design and methods:12-week-old male SHR and Wistar rats were infused through osmotic pumpswith CNP (0,75 µg/hr) or saline (S) for 14 days. Systolicblood pressure (SBP, mmHg) was recorded by tail-cuff method. At the end of thetreatment, the left ventricle (LV) wasextracted to determine left ventricular mass index(LVMI, g LV/mm tibia length), themyocyte area (µm2, Haematoxylin and Eosin-stain), fibrosis (%collagen, Picrosirius Red stain) andinflammation parameters (IL-6 and TNF-α, % stain/mm2by immunohistochemistry, IHC and IL-6, TNF-α and IL-1β, pg/mgprotein by ELISA). Results: Values are means ± SEM. # p<0.01 vs SHR-S. Conclusions: Characteristic high SBP values in SHR areaccompanied by hypertrophy, fibrosis and a higher presence of inflammatorycytokines. Our results show that chronic treatment with CNP attenuates theexpression of proinflammatory markers and the early signs of fibrosis incardiac tissue of hypertensive rats. These effects, combined with the drop inblood pressure we observed, indicate that CNP could possibly have an importantpathophysiological and therapeutical role in preventing or even reversingcardiac fibrosis and inflammation accompanying left ventricular remodelling inarterial hypertension.