The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)