Hypertension and vascular injury: chronic treatment with C-type natriuretic peptide shows beneficial effects on the level of oxidative stress and pro-inflammatory cytokines

ALCOBER, LUCÍA; TOBLLI, JORGE; CANIFFI, CAROLINA; RIPARI, FRANCO; ARRANZ, CRISTINA; GÓMEZ, MARTÍN; GONZÁLEZ MAGLIO, DANIEL

París

Congreso; 26th Meeting of the European Society of Hypertension; 2016

European Society of Hypertension

ObjectiveC -type natriuretic peptide (CNP) and nitric oxide (NO) have effects on the endothelium and the vascular smooth muscle and are considered to be two major factors involved in the regulation of blood pressure and cardiovascular homeostasis. Growing evidence shows that the expression and release of a number of inflammatory cytokines are increased in hypertension and are also present at sites of vascular injury. In addition, pro-inflammatory cytokines such as tumoral necrosis factor alpha (TNF-a) and interleukin 1 (IL-1) stimulate the release of C-type natriuretic peptide (CNP), showing a potential role of CNP as a modulator of the inflammatory process. The aim of the present study was to evaluate the effects of CNP chronic treatment on vascular NO system, oxidative stress and inflammation in spontaneously hypertensive rats (SHR).Design and method12-week-old male Wistar and SHR were infused with CNP (0.75 µg/hr) or saline (S) (osmotic pumps, 14 days). Systolic blood pressure (SBP, mmHg) was recorded by tail-cuff method. After treatment, animals were decapitated and the thoracic aorta artery was removed to determine: protein expression of endothelial NO synthase (eNOS, % relative to actin density) and its phosphorylation in Ser1177 (% relative to eNOS density) by Western blot, superoxide anion production (O2.-, AU/mg dry weight) using lucigenine, content of thiobarbituric acid reactive species (TBARS, nmol/mg protein), IL-6 and TNF-a (% of staining area) by immunohistochemistry, and IL-1þ (pg/mg protein) by ELISA. Statistics: 2 way ANOVA, Bonferroni test ad hoc or t test. n = 6 rats/group except IL-1þ: n = 3 rats/group.ResultsResults are expressed as mean±SEM.Conclusions: Our results show that CNP chronic treatment attenuates the expression of pro-inflammatory markers and oxidative stress in vascular tissue of hypertensive rats. Also, CNP enhances NO system and induces a drop in blood pressure. These beneficial effects could be related to an overall improvement of target organ damage in this model of hypertension.