Skip to main content
. Author manuscript; available in PMC: 2018 Feb 9.
Published in final edited form as: Nat Med. 2016 Nov 14;22(12):1428–1438. doi: 10.1038/nm.4222

Figure 4. Spermidine ameliorates salt-induced hypertension and heart failure in Dahl salt-sensitive rats.

Figure 4

(a) Schematic overview of spermidine administration (starting from the age of 7 weeks) to Dahl salt-sensitive rats fed a high-salt diet (8% NaCl) ad libitum. Cardiovascular parameters (b-k) and renal tissue characteristics (l, m) were recorded at the indicated ages.

(b) Mean arterial blood pressure (MBP) by the non-invasive tail-cuff method. (N=10 rats/group). Red symbols denote the first time point at which there is a non-significant difference in MBP compared to the peak MBP of the group.

(c) Plasma spermidine and ornithine content and global arginine bioavailability ratio (GABR). N=12/12/12, 11/12/12, 11/12/10 (7wk/9wk/9wk+S) rats, left, center and right sub-panels, respectively.

(d, e) Echocardiographic assessment of tibia length-normalized LV mass (LVmass/TL) (d) and the ratio of peak early Doppler transmitral flow velocity (E) to the corresponding myocardial tissue Doppler velocity (E') (e). N=10 rats/group.

(f-k) Representative pressure-volume loops (f), LV end-diastolic pressure (EDP) (g), myocardial stiffness constant for indexed volumes (end-diastolic pressure-volume relationship [EDPVR] βi) (h), tibia length (TL)-normalized lung and liver weights (i), ejection fraction (EF) (j), and ventricular-vascular coupling (VVC) (k). N=10/9/9/10/10 (7wk/14wk/14wk+S/19wk/19wk+S) rats.

(l) Representative micrographs of 9 rats/group analyzed for renal fibrosis in 19-week-old rats, as assessed by picrosirius red collagen staining.

(m) Urinary lipocalin-2 (Lcn-2) levels. N=12/10/10 (7wk/19wk/19wk+S) rats.

***p<0.001, **p<0.01 and *p<0.05 (ANOVA with post-hoc Tukey in panel c, m, Kruskal-Wallis with corrected multiple-comparisons in panel d). Panels b, e, g-k: p-values represent factor (T, treatment; A, age) comparisons by two-way ANOVA (mixed-design in b and e) including 14wk and 19wk groups followed by simple main effects (***p<0.001, **p<0.01, *p<0.05 vs. age-matched control); +++p<0.001, ++p<0.01, +p<0.05 (ANOVA with post-hoc Tukey comparing controls). Dot- and line-plots show means ± s.e.m. For box-and-whisker plots, whiskers show minima and maxima within 1.5 interquartile range.