ROSTAFUROXIN RESTORES THE INCREASED PERIVASCULAR INNERVATION IN RESISTANCE ARTERIES OF HYPERTENSIVE RATS

Abstract

Objective: Ouabain (OUA) inhibiting Na+, K+-ATPase (NKA) activity modulates neurotransmitter release from perivascular innervation (PVI). However, the role of OUA on PVI through NKA/cSRC signalosome pathway is unknown. Thus, we investigated the role of rostafuroxin (ROSTA) treatment, an OUA signalosome pathway antagonist, on PVI of mesenteric resistance arteries (MRAs) from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, mainly on sympathetic and nitrergic PVI participation. Design and method: Five-week after DOCA-salt treatment, rats were allocated into two groups: DOCA-salt treated with ROSTA (1 mg/kg per day gavage, 3 weeks) or vehicle. Male, Wistar rats uninephrectomized were used as normal control (NC). Systolic blood pressure (SBP) was measured weekly by tail-cuff method. Electric field stimulation (EFS), noradrenaline (NA) and sodium nitroprusside (SNP) response-curves were evaluated in isolated MRA without endothelium. Results: ROSTA treatment decreased SBP (42%) compared to DOCA-salt. EFS induced contractile response in MRAs of all groups, while this response was higher in DOCA-salt compared to NC or ROSTA group. EFS-induced contraction was reduced in the presence of alfa-adrenoceptor antagonist (phentolamine, PNT) in all groups, whereas this contractile response was blocked by the association between PNT and suramin (P2-purinergic receptor antagonist) only in NC and ROSTA groups. L-NAME enhanced the contraction induced by EFS; however, this effect was smaller in DOCA-salt rings compared to NC and ROSTA. EFS-induced contraction was abolished in MRAs preincubated with tetrodotoxin (voltage-dependent sodium channel blocker). On the other hand, concentration–response curves to exogenous NA and SNP were unmodified among groups. Conclusions: ROSTA treatment was able to reduce perivascular sympathetic innervation and to increase nitrergic innervation on the contractile response to EFS in MRAs of DOCA-salt rats. These modifications might contribute to the beneficial effects of OUA/NKA/cSRC pathway antagonism on volume-dependent hypertension.