We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.

© 2014 Elsevier Ltd. Social interactions are central to most animals and have a fundamental impact upon the phenotype of an individual. Social behavior (social interactions among conspecifics) represents a central challenge to the integration of the functional and mechanistic bases of complex behavior. Traditionally, studies of proximate and ultimate elements of social behavior have been conducted by distinct groups of researchers, with little communication across perceived disciplinary boundaries. However, recent technological advances, coupled with increased recognition of the substantial variation in mechanisms underlying social interactions, should compel investigators from divergent disciplines to pursue more integrative analyses of social behavior. We propose an integrative conceptual framework intended to guide researchers towards a comprehensive understanding of the evolution and maintenance of mechanisms governing variation in sociality.