Regional angiotensin II production in essential hypertension and renal artery stenosis.
To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 125I-angiotensin I and II and endogenous angiotensin I and II in the aorta and the antecubital, femoral, renal, and hepatic veins during systemic infusion of 125I-angiotensin I or II. Extraction of arterially delivered angiotensin II ranged from 30-50% in the limbs to 80-100% in the renal and hepatomesenteric vascular beds both in essential hypertension (n = 13) and in unilateral renal artery stenosis (n = 7). Across the limbs, 20-30% of arterially delivered angiotensin I was converted to angiotensin II in both groups, and there was no arteriovenous gradient in endogenous angiotensin II. No conversion of arterially delivered angiotensin I was detected across the renal and hepatomesenteric beds, and there was net extraction of angiotensin II from the systemic circulation by these beds. Although regional production of angiotensin I at tissue sites made a significant contribution to its level in the veins, little of this locally produced angiotensin I reached the regional veins in the form of angiotensin II, even in the kidney with artery stenosis, where the venous levels of locally produced angiotensin I were particularly high. These results provide no evidence for a source of circulating angiotensin II other than blood-borne angiotensin I and illustrate the high degree of compartmentalization of angiotensin I and II production.
Admiraal
P J
PJ
Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Danser
A H
AH
Jong
M S
MS
Pieterman
H
H
Derkx
F H
FH
Schalekamp
M A
MA
D000328:Adult; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood / Q000378:metabolism; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012078:Renal Artery Obstruction / Q000150:complications / Q000378:metabolism*; D014018:Tissue Distribution; D014680:Veins
D000804:Angiotensin II; D000803:Angiotensin I