Fate of labeled angiotensin II microinfused into individual nephrons in the rat

Tn, Pullman; Oparil, Suzanne; Fa, Carone

doi:10.1152/ajplegacy.1975.228.3.747

Cited by 38 publications

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“…Consequently one has to be careful with conclusions based on studies with injected ligands. The fact that CT to some extent is taken up and degraded within the cell is different from the degradation pat tern of some other small peptides such as angiotensin [19], bradykinin [20], glucagon (MW == 3,500) [21], and neurotensin [22] which are degraded at the brush border and apparently not taken up to any significant ex tent. The structure of CT containing a ring structure completed by a disulfide bridge is a possible explanation for the greater resistance towards hydrolysis for CT. resulting both in the presence of CT throughout the entire proximal tubule and in a higher extent of in tracellular degradation.…”

Section: Discussionmentioning

confidence: 79%

“…The brush border is used as reference since it is the initial binding site, and since the CT bound at this site can be expected to be mainly intact. Any degradation of CT at the brush border is likely to result in the immediate re lease of the degradation products as it is shown for peptides mainly degraded at this site [19][20][21][22]. Therefore, any CT bound to the brush border can be assumed to be intact or consisting of a few large fragments.…”

Section: Discussionmentioning

confidence: 99%

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Localization and Degradation of Calcitonin in Renal Proximal Tubule of Rat Visualized by Immunocytochemistry

Birn

Christensen²

1993

Kidney Blood Press Res

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Immunocytochemical and cryoultramicrotomy techniques were applied to label endogenous as well as intravenously injected calcitonin (CT) in rat kidney. Endogenous CT was located to the membranes of the brush border, endocytotic invaginations and vacuoles and dense apical tubules suggesting degradation at the brush border and/or within endocytotic vacuoles after glomerular filtration of endogeneous CT There was no labeling at the basolateral membranes indicating that possible basolateral binding sites are of minor quantitative importance in degradation. After injection of human CT there was an additional labeling of lysosomes whereas injection of insulin did not change the labeling pattern for endogenous CT indicating that the uptake of CT involves specific binding sites. Quantitative immunocytochemistry after injection of h-CT applying monoclonal antibodies against two different fragments of CT showed that the relative amounts of these fragments differed in vacuoles and lysosomes from that observed in the brush border, but no difference was seen in dense apical tubules. This suggests that injected CT may be degraded both at the brush border, within endocytotic vacuoles and lysosomes and that some fragments are more sensitive to hydrolysis in lysosomes than others. Furthermore, it indicates an early formation of dense apical tubules before detectable degradation of CT occurs in endocytotic vacuoles.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Localization and Degradation of Calcitonin in Renal Proximal Tubule of Rat Visualized by Immunocytochemistry

Birn

Christensen²

1993

Kidney Blood Press Res

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“…4 Previous studies gave little direct evidence that changes in renal hemodynamics and/or glomerular filtration rate could alter the renal handling of angiotensin II. Pullman et al, 7 in a micropuncture study, found that angiotensin II microinfused directly into the tubular lumen was metabolized rapidly by proximal but not by distal tubules of rats. The design of these experiments did not permit assessment of angiotensin II metabolism in the vascular compartment, the susceptibility of circulating angiotensin II to filtration, or the effects of changes in glomerular filtration rate on the total renal metabolism of angiotensin II.…”

Section: Discussionmentioning

confidence: 99%

“…4 Although there are some data to suggest that factors affecting renal hemodynamics may play a role in the intrarenal metabolism of this peptide, the extent to which changes in renal blood flow or glomerular filtration might modify metabolism is unknown.' 1 - 7 The present study was undertaken to determine whether changes in renal hemodynamics or glomerular filtration rate affect angiotensin II metabolism.…”

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confidence: 99%

Relation of renal hemodynamics to metabolism of angiotensin II by the canine kidney.

Bailie¹,

Oparil²

1977

Circulation Research

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The effects of changes in glomerular filtration rate and renal blood flow on the renal handling of 14 C-or '"l-labeled angiotensin II were studied in pentobarbitai-anesthetized dogs. Labeled angiotension II was injected as a bolus directly into the renal artery 1 and the renal venous effluent was collected. Under control conditions, 52 ± 8% of the labeled material recovered was angiotensin II and the remaining 48 ± 8% consisted of metabolic products. Reducing glomerular filtration rate by increasing ureteral pressure did not change the percentage of label recovered as angiotension II or metabolic products (54 ± 8% and 46 ± 7%, respectively). When renal blood flow was reduced, the percentage of label recovered as angiotensin II fell from 47 ± 6 to 29 ± 7 (P < 0.05) and that as metabolites rose from 46 ± 7 to 61 ± 7 (P < 0.05). The heptapeptide des-1-Asp-angiotensin II (angiotensin III) was not found among the metabolites. The results indicate that reductions in glomerular filtration are not important in intrarenal metabolism of angiotensin II in barbiturate-anesthetized dogs. However, changes in renal blood flow markedly affect angiotensin II metabolism. These observations are compatible with the notion that the intrarenal metabolism of angiotensin II in the dog occurs mainly in the vascular compartment, rather than in the proximal tubule, and can be regulated by alterations in renal blood flow. Failure to demonstrate angiotension III in the renal venous effluent suggests that this peptide is not a major circulating product of intrarenal metabolism of angiotensin II in the dog.ANGIOTENSIN II is rapidly metabolized by multiple enzyme systems collectively called angiotensinases. These enzymes are present in plasma and in several organs including the kidney. 1 " 5 The rate of disappearance of angiotensin II on passage through the kidney is too rapid to be explained by the action of plasma angiotensinases alone and is probably a function of the activity of intrarenal enzymes. 4 Although there are some data to suggest that factors affecting renal hemodynamics may play a role in the intrarenal metabolism of this peptide, the extent to which changes in renal blood flow or glomerular filtration might modify metabolism is unknown.' 1 -7 The present study was undertaken to determine whether changes in renal hemodynamics or glomerular filtration rate affect angiotensin II metabolism. Methods ANIMAL PREPARATION AND EXPERIMENTAL PROTOCOLSMale mongrel dogs weighing 15-20 kg were anesthetized with pentobarbital sodium (30 mg/kg, iv), intubated with a cuffed endotracheal tube, and placed on a Harvard positive-pressure respirator. Both femoral veins were cannulated for the infusion of inulin, saline, and additional anesthetic. A femoral artery was cannulated to measure systemic blood pressure using a strain gauge transducer (Statham P23AA). The left jugular vein was exposed and cannulated with Tygon tubing which was connected to the From the Departments of Human Development and Physiology, Michigan State University, East Lansing. ...

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“…AT4 receptor is also found in the kidney, where this angiotensin-derived fragment can elicit many responses [55] . Aminopeptidases A and N are abundant in the kidney, especially in proximal nephron, and Ang Ⅳ is formed in the glomerulus [56,57] . Ang Ⅳ increases blood flow in the kidney and decreases in Na + transport in proximal tubules [55] .…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

Renin-angiotensin system in the kidney: What is new?

Ferrão

Lara

Lowe

2014

WJN

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The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin Ⅱ (Ang Ⅱ) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱ formation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases. Key words: Renin-angiotensin system; Angiotensin Ⅱ; Kidney; Hypertension treatment; Receptor Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin Ⅱ (Ang Ⅱ)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang Ⅱ synthesis, new Ang Ⅱ metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/ Mas axis, which presents opposite effects of AT1 activation by Ang Ⅱ.

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Fate of labeled angiotensin II microinfused into individual nephrons in the rat

Cited by 38 publications

References 0 publications

Localization and Degradation of Calcitonin in Renal Proximal Tubule of Rat Visualized by Immunocytochemistry

Localization and Degradation of Calcitonin in Renal Proximal Tubule of Rat Visualized by Immunocytochemistry

Relation of renal hemodynamics to metabolism of angiotensin II by the canine kidney.

Renin-angiotensin system in the kidney: What is new?

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