Cardiovascular anti-inflammatory effects of C-type natriuretic peptide in spontaneously hypertensive rats

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

Congreso; 25th European Meeting on Hypertension and Cardiovascular Protection; 2015

Objective: Growing evidence shows that the expression and release of anumber of inflammatory cytokines are increased in hypertension and are alsopresent at sites of cardiovascular fibrosis. In fact, many of theseinflammatory mediators are responsible for the activation of collagen producingfibroblasts. In addition, proinflammatory cytokines such as tumoral necrosisfactoralpha (TNF-a) and interleukin1 (IL1) stimulate the release of C-typenatriuretic peptide (CNP), showing a potential role of CNP as a modulator ofthe inflammatory process. The aim of the present study was to evaluate theeffects of CNP chronic treatment on cardiovascular fibrosis and inflammation inspontaneously hypertensive rats (SHR).SHR-SSHR-CNPSBP-175±3159±5*LVInterstitialcollagen6.81±0.403.27±0.67*Perivascular collagen2.77±0.211.70±0.20*IL-6(IHC)19.4±2.72.1±0.7*TNF-α (IHC)15.7±3.41.5±0.9*IL-1β(ELISA)21.41±1.0814.66±1.19#IL-6 (ELISA)100.10±6.2491.00±11.03TNF-α(ELISA)7.65±0.804.32±0.19#AortaCollagen 34.7±3.519.8±1.7*TGF-β1(IHC)25.1±0.718.5±0.6*IL-6 (IHC)19.2±0.83.4±0.6*TNF-α(IHC)18.5±0.94.4±0.7*Design and method: 12 week old male SHR were infused withCNP (0.75mg/hr) or saline (S) (osmotic pumps, 14 days). Systolic blood pressure(SBP, mmHg) was recorded by tailcuff method. After treatment, animals weredecapitated and theleft ventricle (LV) and thoracic aorta artery were extractedto determine: fibrosis (collagen % by Picrosirius red stain), transforminggrowth factor beta1 ((TGF-b1), %stained area by immunohistochemistry (IHC)) andinflammation parameters (IL-6 and TNF-a, aorta % positive stain area and LV %positive stain/mm2 by IHC and IL6, TNF-a, and IL-1b, pg/mg protein by ELISA).Statistics: t test; SBP, collagen and IHC: n = 6 rats/group; ELISA: n = 3rats/group.Results: Results are expressed as mean±SEM. ∗p < 0.01 vs S; # p <0.05 vs S.Conclusions: Our results show that CNP chronic treatment attenuatesthe expression of proinflammatory markers and the early signs of fibrosis incardiac and vascular tissue of hypertensive rats. These beneficial effectscombined with the drop in blood pressure we observed, could be related to anoverall improvement of target organ damage in this model of hypertension.