Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis.

Abstract

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 [ I] angiotensin I and endogenous angiotensin I during continuous systemic intravenous infusion of monoiodinated [I25 I]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 intrarenai 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 produced 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 intrarenai 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 physiological role of renin, our results support the hypothesis that renin may have such a role. (Hypertension 1990;16:555-563) A ngiotensin II (Ang II) in the kidney subserves / \ important functions in the control of renal A. \ -blood flow, glomerular filtration rate, and tubular sodium handling. It does so by acting on specific receptors located on blood vessels and mesangial and tubular cells. arterially delivered renin or in situ synthesized renin. The interactions between systemically delivered and locally produced components of the renin-angiotensin system in the kidney are not well understood. Detailed information on how much and where Ang I and Ang II are produced in the kidney would help to answer this question.In a previous study in subjects with essential hypertension, we demonstrated that the levels of radiolabeled Ang I in arterial and venous plasma during systemic intravenous infusion of purified monoiodinated [ 125

Regional angiotensin II production in essential hypertension and renal artery stenosis.

“…Thus, because the plasma levels of endogenous Ang I in the aorta have been reported to be only 20% lower than in the right atrium and the peripheral veins, 21 our results indicate that 30-40% of the conversion of blood-borne Ang I occurs outside the lungs. In a similar way (by using Equation 15), it can be calculated that only about 15% of Ang I delivered to the central circulation is degraded into peptides other than Ang II during a single passage of blood from the right atrium to the aorta, whereas 35-50% of Ang I delivered to the systemic circulation is degraded during a single passage of blood from the aorta to the right atrium, indicating that at least 70-80% of the degradation of blood-borne Ang I occurs outside the lungs. We were unable to detect any Ang I-to-II conversion in the kidneys both in URAS and in EHT.…”

“…14 ' 15 In addition, some de novo production of Ang I occurs in circulating plasma by PRA, during the passage of blood from the arterial to the venous side of the vascular bed. Regional venous Ang I derived from arterial delivery could be calculated from the results obtained during infusion of 125 I-Ang I alone as follows:…”

Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats.

“…The lowest values were observed for the 24 hours of the 30th treatment day in the group treated by osmopumps. Because plasma Ang II is not the best index of local production of Ang II and most Ang I and Ang II are produced outside of the plasma, 24 the rise in PRC, which reflects the interruption of the intrarenal feedback loop between Ang II and renin release, may represent a more sensitive index of the degree of RAS blockade. 25 Indeed, PRC was much higher in CI rats, at both day 1 and day 30, especially 24 hours after gavage, which demonstrates a more complete and continuous blockade of the RAS in rats treated by osmopumps.…”

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…In 249 subjects, of which 68% were hypertensive, both systolic and diastolic blood pressure negatively correlated with the renal plasma flow response to Ang II (Perlstein et al, 2004). Admiraal et al (1990) showed the intrarenal RAS activation in patients with essential hypertension by tracer studies. Intravenous infusion of 125 I-Ang I allowed estimation of de novo production of Ang I in the kidney, which corresponded to 80% of the renal venous plasma concentration of Ang I. Estimation of Ang I-to-II conversion in the kidney also demonstrated local synthesis of Ang II (Admiraal et al, 1993).…”