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After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further.

Metal deactivator additives (MDAs) have been used for over 60 years to prevent metal catalyzed reactions in petroleum products; a commonly used metal deactivator is N,N'-disalicylidene-1,2-propanediamine. The quantitation of low MDA concentrations in fuels is challenging due to the complexity of the sample matrix. In this work, this difficulty was overcome using GC × GC hyphenated with a nitrogen chemiluminescence detector. The high resolution power of GC × GC avoided co-elution between the MDA and other sample matrix compounds; while the enhanced sensitivity of GC × GC and the use of a nitrogen chemiluminescence detector supplied a high sensitivity and specificity for nitrogen compounds. For the analysis, the MDA additive was derivatized with the silylation agent N,O-bis (trimethylsilyl)trifluoroacetamide at room temperature and its quantitation was based on an external calibration curve; good linear response was obtained in the 1.4-8.6 ppm range.