Natriuretic peptides and renal inflammation in two models of hypertension: Deoxycorticosterone Acetate-Salt and Renovascular 1 Kidney-1 Clip

KOUYOUMDZIAN NM; RODRIGUEZ FERMEPIN M; CAO G; ROBBESAUL GD; YUN M; DONATO M; FERNÁNDEZ BE; CHOI MR

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias (SAIC-SAI-SAFIS 2020); 2020

SAIC-SAI-SAFIS

Objectives: The aim was to demonstrate the hypothesis that in DOCA-salt (DS) and renovascular 1K-1C (RV) hypertensive models, the development of hypertension and the changes in natriuretic peptides (NP) secretion could be related to simultaneous over expression of NP receptors and inflammatory and fibrotic biomarkers in kidney.Materials: Male Sprague-Dawley rats were randomly divided in three groups: Control (C), DS (30 mg/kg-Salt 1% W/W and RV. After 6 and 12 weeks, systolic blood pressure (SBP) was measured by the tail cuff method; plasma ANP and BNP levels were determined by commercial radioimmunoassay; mRNA expression of receptors NPR-A and NPR-C were measured in kidney by RT-PCR; and immuno-expression of inflammatory biomarkers (IL-6, TNF-α and NFκB) and fibrotic biomarker TGF-β, by immunohistochemistry. Statistical analysis was performed by two-way ANOVA followed by a Tukey-Kramer test.Results: SBP increased in DS and RV at 6 and 12 weeks (mmHg: C6:118+2; DS6:194+2*; RV6:184±2*; C12:121±1; DS12:193±4*; RV12:203±4*). Plasma ANP increased in DS and RV (pg/mL: C6:170+68; DS6:689+143*; RV6:387±90*; C12:87±39; DS12:609±38*; RV12:294±57*), while plasma BNP rose only in RV (pg/mL: C6:39±6; RV6:99±8*; C12:42±7; RV12:94±10*). mRNA levels of NPR-A (AU, C6:0.096±0.011; DS6:0.232±0.015*; C12:0.092±0.020; DS12:0.328±0.039*) and NPR-C (AU, C6:0.184±0.020; DS6:0.721±0.131*; C12:0.131±0.026; DS12:0.302±0.039*) increased only in DS. All biomarkers increased in DS at 6 and 12 weeks (*), while TGF-β and TNF-α enhanced in RV only at 12 weeks (*p<0.05 vs C).Conclusion: Results suggest that ANP is a better marker for volume overload, while BNP level was increased only in the RV model. mRNA expression of both NP receptors increased only in DS and correlated with plasma ANP levels. Furthermore, inflammatory biomarkers expression increased faster in kidney DS than in RV, suggesting that volume overload induces earlier inflammation than pressure overload.