ONLINE MATERIAL

1. ONLINE MATERIAL The improvement after treatment with melatonin was also seen in vessels from CLM without fat (NoF) during hypoxia (ANOVA p<0.05), while in NoF ob/ob the improvement was not statistically significant (Figure 1). In CLM, but not in ob/ob, melatonin decreased contractile responses also in NoF vessels pre-incubated with iberiotoxin (ANOVA p<0.05) (Figure 2).When with fat (WF) vessels were examined, after preincubation with iberiotoxin, vessels from ob/ob treated with melatonin show a reduction of the contractile responses (ANOVA p= 0.036), while in CLM the difference was not statistically significant (p=0.25) (Figure 3). Melatonin treatment did not affect WF vessels from either CLM or ob/ob kept in normoxic conditions (Figure 4).

2. Figure 1 % of KPSS constriction [NA] (Mol/L) Contractility of small arteries without fat (noF) from CLM and ob/ob kept in hypoxic conditions: effect of treatment with melatonin (MEL). CLM: ANOVA p<0.05 hypoxia vs. hypoxia+MEL; ob/ob ANOVA p=NS hypoxia vs. hypoxia+MEL. .

3. Figure 2 % of KPSS constriction [NA] (Mol/L) Contractility of small arteries without fat (NoF) from CLM and ob/ob pre-incubated with iberiotoxin: effect of treatment with melatonin (MEL). CLM: ANOVA p<0.05 NoF+iberotoxin vs. NoF+iberotoxin+MEL; ob/ob ANOVA p=NS NoF+iberotoxin vs. NoF+iberotoxin.

4. Figure 3 % of KPSS constriction [NA] (Mol/L) Contractility of small arteries with fat (WF) from CLM and ob/ob pre-incubated with iberiotoxin: effect of treatment with melatonin (MEL). CLM: ANOVA p=0.25 (NS) WF +iberotoxin vs. WF+iberotoxin+MEL; ob/ob: ANOVA p=0.036 WF +iberotoxin vs. WF+iberotoxin.

5. Figure 4 % of KPSS constriction [NA] (Mol/L) Contractility of small arteries with fat (WF) from CLM and ob/ob: effect of treatment with melatonin (MEL). CLM: ANOVA p=NS WF vs. WF +MEL; ob/ob: ANOVA p=NS WF vs. WF+MEL