Angiotensin I-to-II conversion in the human renal vascular bed

Objective During previous studies in humans and pigs, using infusions of I- 125-angiotensin into the right antecubital vein or the left cardiac ventric le, we were unable to demonstrate conversion of arterial angiotensin I in t he renal vascular bed. The arterial I-125-angiotensin I levels in these stu dies may have been too low to result in detectable renal venous I-125-angio tensin II levels, especially in view of the extensive degradation of angiot ensins in the kidney. To overcome this problem, we now infused I-125-angiot ensin I directly into the renal artery. Design and Methods Five subjects (three women, two men) with essential hype rtension (n = 4) or unilateral renal artery stenosis (n = 1), not treated w ith an ACE inhibitor, were given a 10-min infusion of I-125-angiotensin I ( 3.6 +/- 0.4 x 10(6) cpm/min, mean +/- SEM) into the left (n = 4) or right ( n = 1) renal artery. Blood samples for the measurement of endogenous and ra diolabelled angiotensin I and II were taken under steady-state conditions f rom the aorta and the renal vein of the I-125-engiotensin I-perfused kidney . Results At steady-state, the levels of I-125-angiotensin I in renal venous blood were 5-6 fold lower, and those of I-125-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angioten sin I extraction in the renal vascular bed was calculated to be 80 +/- 3%, of which 9 +/- 1% was due to angiotensin I-to-II conversion. The renal veno us levels of endogenous angiotensin I were 50% higher than its arterial lev els, whereas the levels of endogenous angiotensin II were 50% lower in rena l venous blood than in arterial blood. Taking into consideration the region al metabolism of arterially delivered angiotensins, and the generation of a ngiotensin I in circulating blood by plasma renin activity, it could be cal culated that renal venous angiotensin I is largely derived from renal tissu e sites, and that renal venous angiotensin II has no other sources than art erially delivered angiotensin I and II and angiotensin I generated by plasm a renin activity in the renal vascular bed. Conclusions Less than 10% of arterially delivered angiotensin I is converte d to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiote nsin II in the renal vein, although it is the main source of angiotensin II in renal tissue. Thus, the intrarenal formation of angiotensin II is highl y compartmentalised. J Hypertens 1998, 16:2051-2056 (C) 1998 Lippincott Wil liams & Wilkins.