The Role Of Endogenous Ouabain In The Enhanced Contractile Response To Electrical Field Stimulation In Mesenteric Resistance Arteries From Deoxycorticosterone Acetate-Salt Hypertensive Rats

The Role Of Endogenous Ouabain In The Enhanced Contractile Response To Electrical Field Stimulation In Mesenteric Resistance Arteries From Deoxycorticosterone Acetate-Salt Hypertensive Rats

• Autor
• Ricardo Bernardino de Paula
• Co-autores
• Gisele Kruger Couto , Luciana Venturini Rossoni
• Resumo

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  Ouabain (OUA) inhibit the Na+, K+-ATPase (NKA) activity and activate NKA/cSRC signalosome pathway. Acutely, OUA modulates neurotransmitter release from perivascular innervation (PVI). However, the role of OUA on PVI through signalosome-mediated signalling is unknown. Thus, we investigated the role of rostafuroxin (ROSTA), an OUA signalosome pathway antagonist, on PVI of mesenteric resistance arteries (MRAs) from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats. Five-weeks after DOCA-salt treatment, rats were randomized into two groups: DOCA-salt treated with ROSTA (1 mg/kg/day gavage, 3 weeks) or vehicle. Uninephrectomized male Wistar rats were used as normal control (NC). Blood pressure (BP) was measured weekly by tail-cuff method. Electrical field stimulation (EFS), exogenous NA and sodium nitroprusside (SNP) curves were evaluated in isolated MRA without endothelium assessed in wire myograph. Statistical analysis: Student’s t-test or ANOVA, p<0,05 *vs. NC; #vs. DOCA-salt. Ethical approval n. 03/2016. ROSTA treatment decreased BP (16.5%) as compared to DOCA-salt. EFS-induced contractile response is tetrodotoxin-sensitive in MRA of all groups. This contractile response was higher in MRA of DOCA-salt and ROSTA as compared to NC, while it was lower in ROSTA as compared to DOCA-salt (AUC: NC 49 ± 5.60 (n=29) vs. DOCA-salt 146 ± 15.17* (n=22) vs. ROSTA 98 ± 13.51*# (n=22)). EFS-induced contraction was reduced by the a-adrenoceptor antagonist, phentolamine, in all groups, but suramin (P2-purinergic receptor antagonist) reduced it only in DOCA-salt MRAs. Moreover, the contractile response to EFS was blocked by association among phentolamine, suramin and BIBP3226 (Y1 receptor antagonist) in all groups. In a similar magnitude, L-NAME enhanced EFS-induced contraction in MRA of all groups. Concentration–response curves to NA and SNP were unmodified among groups. These data suggest that ROSTA treatment partially decreased contractile response to EFS in MRAs from DOCA-salt rats through reduced sympathetic components of PVI.

• Palavras-chave
• DOCA-salt, Ouabain, Perivascular Innervation
• Modalidade
• Pôster
• Área Temática
• Sistema endócrino e doenças vasculares