Estimation of regional metabolism and production of angiotensins in hypertensive subjects.

1. We attempted to collect information on the metabolism and production of angiotensins (ANG) in different vascular beds in humans by constant i.v. infusion of mono-iodinated [125I]-ANG I into subjects with essential hypertension, at the time of renal vein catheterization as part of the diagnostic work-up for renovascular hypertension. 2. Blood samples were taken from the aorta and the renal, antecubital, femoral and hepatic veins. ANG I, ANG II, [125I]-ANG I and [125I]-ANG II were extracted from plasma, separated by h.p.l.c. and quantitated by radio-immunoassay or gamma counting. 3. Our studies so far are restricted to subjects on captopril 50 mg twice daily. Under ACE inhibition (4-6 h after dosing of captopril) no differences in elimination half-life and regional extraction were found between infused [125I]-ANG and unlabelled ANG I. Extraction of arterially delivered [125I]-ANG I was 80% in the kidney, 45% in the forearm, 58% in the leg and 95% in the hepato-mesenteric vascular bed. 4. Measurements of arterial and venous [125I]-ANG II levels indicated that [125I]-ANG I-II conversion had occurred in the cardio-pulmonary vascular bed. 5. ANG I production in the hepato-mesenteric region could be largely accounted for by the renin activity of circulating plasma, but in kidney and limbs only 20-30% of regionally produced ANG I could be accounted for by plasma renin activity. 6. Thus, a major fraction of regionally produced ANG I appears to be formed locally, i.e. not in circulating plasma.(ABSTRACT TRUNCATED AT 250 WORDS)