OBJECTIVE: During previous studies in humans and pigs, using infusions of 125I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125I-angiotensin I directly into the renal artery. DESIGN AND METHODS: Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n = 1), not treated with an ACE inhibitor, were given a 10-min infusion of 125I-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 radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125I-angiotensin I-perfused kidney. RESULTS: At steady-state, the levels of 125I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin 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 venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. CONCLUSIONS: Less than 10% of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin 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 highly compartmentalised.
OBJECTIVE: During previous studies in humans and pigs, using infusions of 125I-angiotensin into the right antecubital vein or the left cardiac ventricle, we were unable to demonstrate conversion of arterial angiotensin I in the renal vascular bed. The arterial 125I-angiotensin I levels in these studies may have been too low to result in detectable renal venous 125I-angiotensin II levels, especially in view of the extensive degradation of angiotensins in the kidney. To overcome this problem, we now infused 125I-angiotensin I directly into the renal artery. DESIGN AND METHODS: Five subjects (three women, two men) with essential hypertension (n = 4) or unilateral renal artery stenosis (n = 1), not treated with an ACE inhibitor, were given a 10-min infusion of 125I-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 radiolabelled angiotensin I and II were taken under steady-state conditions from the aorta and the renal vein of the 125I-angiotensin I-perfused kidney. RESULTS: At steady-state, the levels of 125I-angiotensin I in renal venous blood were 5-6 fold lower, and those of 125I-angiotensin II were 4-5 fold higher than in renal arterial blood. On the basis of these levels, angiotensin 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 venous levels of endogenous angiotensin I were 50% higher than its arterial levels, whereas the levels of endogenous angiotensin II were 50% lower in renal venous blood than in arterial blood. Taking into consideration the regional metabolism of arterially delivered angiotensins, and the generation of angiotensin I in circulating blood by plasma renin activity, it could be calculated that renal venous angiotensin I is largely derived from renal tissue sites, and that renal venous angiotensin II has no other sources than arterially delivered angiotensin I and II and angiotensin I generated by plasma renin activity in the renal vascular bed. CONCLUSIONS: Less than 10% of arterially delivered angiotensin I is converted to angiotensin II in the renal vascular bed. Conversion of angiotensin I generated at renal tissue sites does not contribute to the level of angiotensin 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 highly compartmentalised.
Authors: R Folgert G Haverdings; Marijke Haas; Gerjan Navis; Anne-Miek Van Loenen-Weemaes; Dirk K F Meijer; Dick De Zeeuw; Frits Moolenaar Journal: Br J Pharmacol Date: 2002-08 Impact factor: 8.739
Authors: L Gabriel Navar; Kenneth D Mitchell; Lisa M Harrison-Bernard; Hiroyuki Kobori; Akira Nishiyama Journal: J Renin Angiotensin Aldosterone Syst Date: 2001-03 Impact factor: 1.636
Authors: Juan Carlos Q Velez; Kevin J Ryan; Caroline E Harbeson; Alison M Bland; Milos N Budisavljevic; John M Arthur; Wayne R Fitzgibbon; John R Raymond; Michael G Janech Journal: Hypertension Date: 2009-03-16 Impact factor: 10.190