Introduction. Brain derived natriuretic peptide (BNP) is a cardioprotective peptide released - together with the inactive N-terminal part of its prohormone, NT-proBNP - in response to different kinds of myocardial stress. Hypoglycemia and hypoxemia are conditions which threaten cellular function and hence potentially stimulate BNP release. BNP interacts with the renin angiotensin system (RAS). The aim of this study was therefore to explore if basal RAS activity has impact on NT-proBNP concentrations during myocardial stress induced by hypoglycemia and hypoxemia. Methods. From a cohort of 303 healthy young men, 10 subjects with high RAS activity and 10 subjects with low RAS activity (age 26 ±1 years; mean ±SE) were studied in a single-blinded, randomized, counter-balanced, cross-over study on three occasions separated by at least three weeks: 1) hypoglycemia (mean nadir p-glucose 2.7 ±0.5 mmol/l), 2) hypoxemia (mean nadir pO2 5.8 ±0.5 kPa), and 3) normoglycemic normoxia (control). NT-proBNP was measured at baseline, during the stimuli, and in the recovery phase. Results. Hypoxemia was associated with a 9% increase in NT-proBNP from 18.6 ±12.7 pg/ml at baseline to 20.3 ±12.7 pg/ml during hypoxemia (p<0.001). Hypoglycemia did not affect the NT-proBNP level. RAS activity had no impact on NT-proBNP levels during hypoglycemia and hypoxemia. Conclusion. Hypoxemia - but not hypoglycemia - stimulates NT-proBNP. This indicates that cardiac defense mechanisms against hypoglycemia, if any, are probably different from those against hypoxemia. Basal RAS activity had no impact on NT-proBNP levels.