metabolism. ANP and BNP induced natriuretic peptide receptor A activation potently stimulates adipose tissue lipolysis through cGMP and protein kinase G activation. The mechanism cannot explain protective natriuretic peptide influences on glucose metabolism. Instead, natriuretic peptide may promote adiponectin production, an adipokine with insulin sensitizing properties. ANP augmented adiponectin production and release from cultured human adipocytes. In heart failure patients, therapeutic ANP infusions increased total and high molecular weight adiponectin levels. Studies in heart failure patients could be confounded by the AG-221 underlying pathology. The heart failure-associated neurohumoral activation may be particularly important in this regard. Heart failure medications including beta-adrenoreceptor blockers and renin-angiotensinaldosterone system inhibitors could also affect natriuretic peptide mediated responses. Therefore, we tested the hypothesis that ANP acutely increases adiponectin levels in healthy men. Methods The local ethics committee approved the study and writteninformed consent was obtained. We included 12 healthy men receiving no medications. After an overnight fast, we placed one catheter each into large antecubital veins of both arms. We used one catheter for infusion and the other one for blood sampling. We inserted a microdialysis probe into abdominal subcutaneous adipose tissue to monitor changes in tissue lipolysis and blood flow. After at least 60 min resting phase, an incremental administration of human ANP with a maximal rate of 25 ng/kg/min and a total infusion time of 135 min commenced as described previously while blood pressure was closely monitored. ANP concentrations ANP and Adiponectin were determined using a radioimmunoassay. Total and HMWadiponectin plasma concentrations were measured using multimeric ELISA. We monitored ANP-induced changes in adipocyte lipolysis through plasma and microdialysate glycerol measurements. To exclude a time effect, we also obtained venous blood samples in 7 healthy age and BMI-matched men at identical time points without ANP infusion. Two tailed, one sample t-test and linear regression analysis were used to compare changes in adiponectin with ANP infusion and to establish associations between ANP, adiponectin and metabolic parameters, respectively. Changes between groups were compared by student’s t-test. Data are expressed as mean6SEM. Results Plasma ANP was 4165 pg/mL at baseline and increased to 447629 pg/mL at the end of the ANP infusion. During ANP infusion, systolic blood pressure decreased from 11663 mm Hg at baseline to 11062 mm Hg at the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/2221058 end of ANP infusion. Diastolic blood pressure was 6262 mm Hg at baseline and did not change significantly with ANP infusion. Venous glycerol concentration increased from 4865 mmol/L at baseline to 81680 mmol/L with ANP infusion. Dialysate glycerol in adipose tissue increased 
from 5166 mmol/L at baseline to 90614 mmol/L with ANP infusion while the ethanol ratio did not change. Thus, ANP was sufficiently dosed to affect adipose tissue function. Total adiponectin was 5.660.5 pg/ml at baseline and increased by 1465% with ANP infusion. HMW-adiponectin, the most potent isoform in terms of insulin sensitization, was 2.960.3 pg/ml at baseline and increased by 1365% with ANP. The change in HMWadiponectin was directly correlated with the change in plasma ANP with ANP infusion. Changes in adipose tissue glycerol and HMW-adiponectin with ANP infus