Conversion of Angiotensin I into Angiotensin II in the Isolated Perfused Rat Kidney

Hofbauer, K. G.; Zschiedrich, H.; Rauh, W; Gross, F.

doi:10.1042/cs0440447

Cited by 56 publications

(30 citation statements)

References 13 publications

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“…This possibility, however, is unlikely in view of the reported failure of a competitive antagonist of angiotensin II to affect renal blood flow and sodium excretion in normal dogs (19). Similarly, direct actions of BPP 9a on the kidney are also unlikely, since this agent fails to produce vasodilation in the isolated rat kidney perfused with an artificial medium devoid of kininogen (20). Therefore, the effects of BPP 9a on canine renal blood flow and salt-water excretion appear to be related to kininase II inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Since the vasodilator, diuretic, and natriuretic actions of bradykinin were observed only during infusion of the peptide, several doses of the agent could be infused in the same dog by alternating periods of bradykinin infusion with periods of saline infusion (30 minutes). In one group of nine dogs five different doses of bradykinin (10,20,50, 100 and 200 ng/kg min-') were infused into the renal artery for periods of 10 minutes each. The kinin content of renal venous blood was determined on samples obtained during the fifth minute of infusion and used to calculate the survival of bradykinin on passage across the kidney.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.

Nasjletti¹,

Colina-Chourio²,

McGiff³

1975

Circulation Research

138

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In chloralose-anesthetized dogs, we investigated the disappearance of bradykinin on passage across the renal circulation. The peptide was infused into a renal artery at various doses (5-200 ng/kg min~'); renal blood flow and the concentration of kinins in renal venous blood were then determined and the percent survival of bradykinin on passage through the kidney calculated. Bradykinin caused a dose-related increase in renal blood flow, urine flow, sodium excretion, and kinin content of renal venous blood. Intravenous administration of BPP 9cr (300 /ig/kg), a peptide kininase II inhibitor, potentiated the renal vasodilator, diuretic, and natriuretic actions of bradykinin and augmented the survival of the kinin on passage through the kidney from 12.72 ± 1.64% in control dogs to 53.92 ± 7.48% (P < 0.001). Furthermore, the values of peptide survival were positively correlated with the increases in renal blood flow (r = 0.92, P < 0.01), urine flow (r = 0.75, P < 0.01), and sodium excretion (r = 0.68, P < 0.01) produced by bradykinin. In addition, BPP 9a by itself increased renal blood flow (16%, P < 0.01), urine flow (115%, P < 0.005), and sodium excretion (167%, P < 0.02). Similarly, the concentration of kinin in renal venous blood and the excretion of urinary kinins rose from 0.11 ± 0.03 ng/ml and 4.4 ± 1.1 ng/min to 0.24 ± 0.05 ng/ml (P < 0.005) and 38.5 ± 12.2 ng/min (P < 0.02). These studies suggest that kinins generated intrarenally play a role in the regulation of renal blood flow and salt-water excretion and that variations in the capacity of the kidney to inactivate kinins may be a determinant of the intrarenal activity of the kallikrein-kinin system.• The demonstration that urine contains large amounts of kinins (1) and an active kallikrein indistinguishable from the active form of renal kallikrein (2) suggests that kinins may be generated within the kidney. Since this organ is also a rich source of kininases (3), the intrarenal activity of the kallikrein-kinin system is probably a function of both kinin-generating and kinin-inactivating mechanisms. The importance of the latter cannot be overlooked when one is considering the local activity of hormones that are as readily inactivated by renal enzymes as are kinins. In comparison to other tissues, the kidney is one of the richest sources of kininases; it has at least three types of kinin-inactivating enzymes (3). Because these enzymes are predominantly located in subcellular structures (3), the in vitro inactivation of kinin by a renal extract may bear no relationship to the in This work was supported by U. S. Public Health Service Grants HL 15791 and HL 13624 from the National Heart and Lung Institute, by American Heart Association Grant 73720, and by the Wisconsin Heart Association.Dr. McGiff is a Burroughs Wellcome Fund Scholar in Clinical Pharmacology. Dr. Colina-Chourio is the recipient of a fellowship from the University of Zulia, Maracaibo, Venezuela.Received January 16, 1975. Accepted for publication April 11, 1975. vivo inactivation of t...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.

Nasjletti¹,

Colina-Chourio²,

McGiff³

1975

Circulation Research

138

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“…In the isolated perfused rat kidney, Ang I had to be infused in a 50 times higher molar dose than Ang II to induce the same vasoconstrictor response. 31 Thus, there was apparently some intrarenal conversion of arterially delivered Ang I, but only to a very limited degree.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 1993

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To study regional metabolism and production of angiotensin II, we measured steady-state plasma levels of 12S I-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 125 I-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. sin system, circulating renin acts on circulating .Z \ -angiotensinogen to form the decapeptide angiotensin I (Ang I). During the passage of blood through the lungs, Ang I is converted to the octapeptide angiotensin II (Ang II) by angiotensin converting enzyme (ACE) that is bound to the luminal surface of the pulmonary vascular endothelium. Ang II is then transported by the bloodstream to peripheral target sites to exert its physiological actions.This view of the renin-angiotensin system, however, is an oversimplification. Observations in animals and humans have clearly demonstrated that considerable conversion of plasma Ang I occurs in organs other than the lungs,'-6 but particularly in humans, it is not known to what extent extrapulmonary conversion of Ang I to Ang II contributes to the circulating levels of Ang II.Moreover, the concept of the renin-angiotensin system as a circulating endocrine system is now being challenged.7 -10 Animal studies, in which pharmacological doses of Ang II were systemically infused, have

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“…After anesthesia with sodium pentobarbital (50 mg/kg, ip) the kidney was surgically isolated and perfused with modifications of the technique previously described by Hofbauer et al (1973). The right kidney was perfused through a catheter placed into the distal aorta and advanced to the origin of the right renal artery.…”

Section: Isolation and Perfusion Of The Kidneymentioning

confidence: 99%

Significance of sodium, sympathetic innervation, and central adrenergic structures on renal vascular responsiveness in DOCA-treated rats.

Berecek¹,

Murray²,

Gross³

1980

Circulation Research

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SUMMARY The effects of sodium, sympathetic innervation, and central adrenergic structures on the development of changes in renal vascular reactivity were studied in unilaterally nephrectomized rats treated with a single implant of deoxycorticosterone acetate (DOCA; 100 mg/kg). Vascular reactivity to norepinephrine (NE) and vasopressin (ADH) was assessed in isolated kidneys perfused with a synthetic medium. Influence of sodium was determined by placing DOCA-treated rats on high, normal, and low sodium intakes. Neural influence was studied by means of local denervation of the renal artery and by intravenous (iv) and intraventricular (ivt) administration of 6-hydroxydopamine (6-OHDA). Marked changes in renal vascular reactivity in DOCA-treated rats were already apparent prior to the rise in blood pressure. Dose-response curves for NE and ADH showed parallel leftward shifts and decreased threshold doses. Normal sodium intake, local denervation, and peripheral sympathectomy had no effect on the development of these vascular changes in DOCA-treated rats. However, sodium deficiency and ivt administration of 6-OHDA totally prevented development of enhanced vascular reactivity. These results imply that increased vascular reactivity is a major factor in the development of DOCA-hypertension. Circ Res 47: 675-683, 1980

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Conversion of Angiotensin I into Angiotensin II in the Isolated Perfused Rat Kidney

Cited by 56 publications

References 13 publications

Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.

Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.

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

Significance of sodium, sympathetic innervation, and central adrenergic structures on renal vascular responsiveness in DOCA-treated rats.

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