Table E1 – Sequences of primers used in qPCR experiments Forward Reverse Human Mineralocorticoid receptor (NR3C2) GAGGCTTCAGGATGCCATTA TCTGCAAGCAGGACAATTCTT Glucocorticoid receptor (NR3C1) AGAAAACTCCAGCCAGAACTG GATTTCAGCTAACATCTCGGGGA 18S GGACACGGACAGGATTGACA ACCCACGGAATCCAGAAAGA Alpha 1 D adrenoceptor TCTGCTGGTTCCCTTTCTTC CACGCAGCTGTTGAAGTAGC Mouse Mineralocortcoid receptor (NR3C2) CCAGAAGAGGGGACCACATA GGAATTGTCGTAGCCTGCAT TTCGCAGGCCGCTCAGTGTT TTGGGAGGTGGTCCCGTTGCT α1-a adrenoceptor GCGGTGGACGTCTTATGCT TCACACCAATGTATCGGTCGA α1-b adrenoceptor CCT GGTCATGTACTGCCG GACTCCCGCCTCCAGATTC α1-d adrenoceptor AGTTGGTGACCGTCTGCAAGT CGCTGTGGTGGGAACCGGCAG Endothelin 1 receptor A CCCAAACCTCCCAAGTCTCTC TGGAAATGACATGGGCGGTAT Angiotensin II Receptor type 1 GACTGGATGATGCTGTCTGGC CTTGGAGGGTTGCTGTGAGT CGCCGCTAGAGGTGAAATTC TCTTGGCAAATGCTTTCGC Table E1 – Sequences of primers used in qPCR experiments

  Control LPS LPS-Aldosterone p SBP EC50 (mg/kg) 0.020±10-3 0.019±10-3 0.022±1.2x10-3 ns Emax (mmHg) 38.15±2.1 31.03±2.5 33.23±2.6 DBP 0.016±10-3 0.009±10-3 0.013±10-3 38.97±1.9 28.63±2.7 30.29±2 0.037* Table E2 – Effect of Aldosterone on Blood Pressure response to Phenylephrine in Endotoxic Shock. Systolic and Diastolic response to increasing doses of phenylephrine. Results are expressed as mean±SD *Multiple comparison test: p ≤ 0.05 in all cases

  Control LPS LPS-Aldosterone p EC50 (Log M) 5.1 10-7±5 10-9 5.7 10-7±6 10-9 4.4 10-7±5 10-9 0.03# Emax 1 1±0.2 0.55±0.1 0.78±0.3 0.002## Table E3 – Effect of Aldosterone on ex vivo first-order mesenteric artery contractile response to phenylephrine in endotoxemic mice Dose-response curve parameters. Results are expressed as mean±SD. Vessels were studied 18 hours after LPS (15 mg/kg) and Aldosterone (A mg/kg) injection. n = 1 Normalized on control #Multiple comparison test: p<0.05 for LPS vs Control, and LPS-Aldosterone vs LPS ## Multiple comparison test p<0.05 in all cases

Table E4 – Brief patient and control subject characteristics   Age Gender SAPSII Medical history Medications Site of infection Microorganism Outcome Patient 1 77 M 56 Rectal adenocarcinoma None Soft tissue Escherischia coli Discharged Patient 2 69 42 Aortic valve replacement warfarin Abdomen (pancreatitis) NA Dead in ICU Patient 3 55 50 Myasthenia gravis, thymoma Prednisone, azathioprine, neostigmine Lung Patient 4 44 F 35 Seizures levetiracetam Patient 5 45 Abdomen E. coli and E. faecalis Patient 6 58 COPD Salbutamol, ipratropium Str. Peunomniae Patient 7 32 Chronic sinusitis, ethanol abuse CNS (meningitis) Str. Pneumoniae Control 1 66 - Control 2 Control 3 Control 4 40 Control 5 38 Asthma in infancy Control 6 29 Appendicectomy Levonorgestrel Control 7 59 Table E4 – Brief patient and control subject characteristics

Figure E1 – Effect of Aldosterone on vasoconstrictor receptor expression in endotoxemic mouse aortas. MR and GR mRNA expression in mouse aortas 18 hours after LPS or LPS-Aldosterone injection. Mice were injected intraperitoneally with LPS (15 mg/kg) and Aldosterone (1mg/kg) (n=5 mice per group, * p ≤ 0.05 vs Control, #p ≤vs LPS)

Figure E2 – MR and GR expression in endotoxemic mice aortas Figure E2 – MR and GR expression in endotoxemic mice aortas. MR and GR mRNA expression in mouse aortas 6 hours after LPS or LPS-Aldosterone injection. Mice were injected intraperitoneally with LPS (15 mg/kg) and Aldosterone (1mg/kg) (n=5 mice per group, * p ≤ 0.05 vs Control, #p ≤vs LPS)

Figure E3 – MR expression in HUVECs treated with LPS Figure E3 – MR expression in HUVECs treated with LPS. MR mRNA expression in HUVECs 5, 10 and 24 hours after incubation with LPS (n=5 replicates per group)

* Figure E4 –MR and GR mRNA expression in HUVECs treated with pro-inflammatory cytokines. Cells were incubated with TNF-α (100 ng/ml), IL1-β (50 ng/ml) and IFN-γ (500UI/ml) during 5 hours. (n=6 replicates per condition,* p≤0.05 vs Control)

Figure E5 – Time-course and dose-response of MR expression downregulation by TNF-alpha in HUVECs. Panel A - MR mRNA expression in HUVECs 75 to 450 min after incubation with TNF-α (100 ng/ml). Panel B – MR mRNA expression in HUVECs 5 hours after incubation with TNF-α (0.01 to 100 ng/ml) (n=5 replicates per condition, * p≤0.05 vs control) *

ns Figure E6 - GR mRNA expression in HUVECs treated with TNF-α and BAY 11-7082. GR mRNA expression five hours after treatment with TNF-alpha (10 ng/ml) . (n=6 replicates in all groups)

Figure E7 – Effect of NF-kappa B inhibitor BAY 11-7082 on MR mRNA expression down regulation by plasma from septic patients Cells were pre-incubated with BAY 11-7082 (10 µM) and incubated with septic/control plasma for 5 hours (n= 3 subjects per group, 3 replicates per condition, *p≤0.05 vs Control, #p≤0.05 vs patients)