INTRARENAL DENOVO PRODUCTION OF ANGIOTENSIN-I IN SUBJECTS WITH RENAL-ARTERY STENOSIS

To estimate the renal extraction and de novo production of angiotensin I and to assess the contribution of blood-borne renin to renal angiotensin I production, the aortic and renal venous plasma levels of renin and intact [125I]angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [125I]angiotensin I were measured in subjects with unilateral renal artery stenosis (n = 8) who were treated with captopril (50 mg b.i.d.). Results demonstrated that 80% of angiotensin I delivered by the renal artery was extracted both by the affected and the unaffected kidney and that on both sides a major part of angiotensin I in the renal vein was derived from intrarenal de novo production. Production of plasma angiotensin I was in excess over extraction (p < 0.01) on the affected side, whereas extraction was in excess over production (p < 0.01) on the contralateral side. The plasma level of de novo intrarenally producted angiotensin I in the renal vein was seven times higher on the affected side than the contralateral side. This difference was by far too big to be explained by a difference in the transit time of blood between the two kidneys, by an augmented production of angiotensin I in the circulating blood passing through the affected kidney due to the higher level of venous plasma renin activity in that kidney, or by the combination of both. We conclude that intrarenal production of angiotensin I in a compartment outside the circulating blood is a major source of this peptide in the renal vein, and that in kidneys with artery stenosis in situ, synthesized renin is an important component of this source. To the extent that local angiotensin I production by intrarenally synthesized renin is a sine qua non for a local physiologial role of renin, our results support the hypothesis that renin may have such a role.