Metabolic effects of C-type natriuretic peptide: impaired responses in oxidative stress and adipose tissue in spontaneously hypertensive rats

RIPARI, FRANCO; ARRANZ, CRISTINA; CANIFFI, CAROLINA; MAFKA, MAILÉN; ALCOBER BOQUET, LUCÍA; MORALES, CELINA

Milán

Congreso; 27th European Meeting on Hypertension and Cardiovascular Protection; 2017

European Society of Hypertension

Objective:Atrial and brain natriuretic peptides promote lipid degradation and energy dissipation, with an inverse relationship between the levels of these peptides and the presence of overweight and obesity. Also, C-type natriuretic peptide (CNP) was described as an anorexigenic peptide at central level. However, evidence of CNP effects on the energy balance, whether direct or through other systems, are limited. In previous results, we show that chronic CNP administration improves vascular function, stimulating endothelial nitric oxide (NO) system and decreasing vascular oxidative stress in hypertensive states. The aim of the present study was to evaluate the effects of chronic CNP treatment on systemic oxidative stress and adipose tissue content in normotensive and spontaneously hypertensive rats (SHR). Design and method:12-week-old male Wistar and SHR were infused with CNP (0.75 g/hr) or saline (S) (osmotic pumps, 14 days). Systolic blood pressure (SBP, mmHg) was recorded by tail-cuff method. Animals were fed standard rat chow and tap water ad libitum. After treatment, plasma samples were collected to determine the content of: thiobarbituric acid reactive species (TBARS, nmol MDA/mL) and gluthatione (GSH, mol/L); and urine samples were collected to measure excretion of nitrites and nitrates (NOx, end products of NO metabolism, nmol/min.100g body weight). Animals were decapitated and both epididymal and retroperitoneal adipose tissues (EAT and RAT, respectively) were removed and weighted (g/100 g body weight), and adipocyte area (AA, ²) was measured in hematoxylin-eosin stained slices. Statistics: 2 way ANOVA, Bonferroni test ad hoc. n = 4 rats/group.Results:Wistar-SWistar-CNPSHR-SSHR-CNPSBP119±5121±4187±3*158±6#BW344±8347±12335±6331±12TBARS1.3±0.21.4±0.113.2±1.0*11.7±1.3GSH129±17256±34*100±15197±28#NOx1.10±0.111.63±0.12*1.64±0.12*1.73±0.09EAT1.33±0.111.13±0.090.84±0.06*0.91±0.04RAT0.68±0.110.41±0.04*0.73±0.080.72±0.08EAA4663±3883260±310?5960±431?4855±266?* p < 0.01 vs. Wistar-S; # p < 0.01 vs. SHR-S; ? p < 0.05 vs. Wistar-S; ? p < 0.05 vs. SHR-S.Conclusions:Our results show that chronic CNP treatment improved content of plasmatic GSH and urinary excretion of NOx in normotensive rats. SHR showed higher leveles of SBP and plasmatic oxidative stress. Chronic CNP administration decreased SBP, but did not modify the content of TBARS in plasma in SHR. In addition, chronic treatment with CNP decreased the content of adipose tissue in both groups. However, this effect was more marked in adipose tissue of normotensive rats. An altered response to CNP in adipose tissue could be related to these results in SHR.