The effect of chronic bilateral nephrectomy on plasma and brain angiotensin

Mr, Trolliet; Mi, Phillips

doi:10.1097/00004872-199201000-00006

Cited by 27 publications

(16 citation statements)

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“…Indeed, recent work now proposes a role of angiotensin II as a tissue or paracrine hormone (Vinson et al, 1995a), and our own studies on the distribution of the ATI receptor confirm this. In brief, several localized tissue reninangiotensin systems have been described, particularly in the adrenal gland, uterus (Capponi and Catt, 1980), heart (Okura et al, 1992), pituitary and brain (Mendelson et al, 1984;Trolliet and Phillips, 1992). In the present context, it is therefore pertinent that significant levels of angiotensin-converting enzyme activity have been measured in human breast tissue (Dzau, 1993).…”

Section: Discussionmentioning

confidence: 95%

Angiotensin II type 1 receptor expression in human breast tissues

Inwang

Puddefoot²,

Brown³

et al. 1997

Br J Cancer

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Summary We demonstrate the expression of angiotensin 11 type 1 (AT1) receptors in normal and diseased human breast tissues. Using monoclonal antibody 6313/G2, directed against a specific sequence in the extracellular domain of the AT1 receptor, immunocytochemical analysis revealed positive immunoreactivity in membrane and cytoplasm of specific cell types. Immunoblotting of solubilized proteins separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) from benign and malignant tumours identified a single immunoreactive species with a molecular mass of approximately 60 kDa, consistent with that of the mature glycosylated receptor. In studies of [1251]angiotensin 11 binding using breast membrane preparations, concentrations of specific angiotensin 11 binding sites were found to range from 1.8 to 100 fmol mg-' protein, with a Kd of approximately 60 nm. Most of the specifically bound [1251]angiotensin II was displaced by losartan, a specific angiotensin 11 type 1 receptor antagonist, while less was displaced by the AT2 receptor type antagonist, CGP42112A, thus confirming the prevalence of AT1 receptors in this tissue type. These data suggest that the renin-angiotensin system may be involved in normal and abnormal breast tissue function.Keywords: breast cancer; renin-angiotensin system; losartan; immunocytochemistry; monoclonal antibody G313/G2 Angiotensin II plays a central role in mammalian electrolyte homeostasis and blood pressure control (Peach, 1977;Vinson et al, 1992). Two main subtypes of angiotensin II receptors, designated types 1 and 2 (ATl and AT2), have been recognized, but the majority of the well-known actions of angiotensin II occur via the ATI subtype (Herblin et al, 1991;Ouali et al, 1992). Local tissue renin-angiotensin systems have been demonstrated in several tissues, and in some cases it has been suggested that local production of angiotensin II may be particularly concerned in trophic actions (Vinson et al, 1995a).The availability of our recently developed monoclonal antibody (6313/G2) to the ATI receptor subtype (Barker et al, 1993a) has facilitated the further study of its distribution (Vinson et al, 1995a). We describe here studies investigating the presence of the ATl receptor in normal and diseased breast. Sections were then immersed in endogenous peroxidase blocking solution (3 ml of 100 volume hydrogen peroxide and 97 ml of methanol; 15 min), washed in tap water (10 min) and distilled water (5 min). Sections were immersed in 10 mm citrate buffer, pH 6.0, covered loosely with 'Saranwrap' (Dow Chemical Co.) and boiled in a microwave oven for 10 min at 630 w (H2500 BioRad, Watford, Herts., UK). After standing for 10 min in hot buffer, sections were washed in tap water (5 min) and transferred to 0.05 M Tris-buffered saline, pH 7.6 (TBS). MATERIAL AND METHODSTissue sections were then incubated with normal rabbit serum (Dako, High Wycombe, Bucks., UK) diluted 1:5 in Tris-buffered saline (20 min) and incubated (60 min) with mouse primary antibody 6313/G2 (Barker et al, 1...

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Section: Discussionmentioning

confidence: 95%

Angiotensin II type 1 receptor expression in human breast tissues

Inwang

Puddefoot²,

Brown³

et al. 1997

Br J Cancer

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“…It has also been proposed that local renin synthesis, e.g., in vessel walls, is suppressed by circulating renin, which almost exclusively originated from the kidneys. Hence, elimination of circulating renin might boost local renin synthesis (19,20,31).…”

Section: Discussionmentioning

confidence: 99%

Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats

Pedersen

Paulson²,

Nielsen³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats. Am J Physiol Heart Circ Physiol 285: H1097-H1104, 2003. First published May 15, 2003 10.1152/ajpheart.00098. 2003.-The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133 Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensinconverting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 Ϯ 4 mmHg) and sham-operated (58 Ϯ 4 mmHg) rats compared with diet control rats (78 Ϯ 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 Ϯ 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls. renin-angiotensin system; nephrectomy; captopril CEREBRAL BLOOD FLOW (CBF) is autoregulated, i.e., kept constant over a wide range of blood pressure. Autoregulation is mainly a feature of the smaller cerebral resistance vessels (4,(6)(7)(8)17). Blockade of the reninangiotensin system by angiotensin-converting enzyme (ACE) inhibitors, e.g., captopril (2, 3, 30), shifts both the lower and upper limits of CBF autoregulation toward lower blood pressure, possibly by releasing angiotensin II-mediated tone in the larger cerebral resistance vessels (21), with a contribution of bradykinin accumulation (27). Angiotensin II subtype 1 (AT1) receptor antagonists and agonists also shift the limits of CBF autoregulation (15,26,33). Modulation of the angiotensin II AT2 receptors appears to have limited influence on CBF autoregulation (5, 15, 26).The renin-angiotensin system may influence CBF autoregulation from the circulating blood or by in situ vessel wall activity of components of the system (14). The aim of the present study was to investigate the influence of circulating versus local renin on CBF and its autoregulation. The study was carried out in nephrectomized dialyzed rats in which no circulating renin was present. The animals were studied with or without captopril blockade and compared with ...

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“…In addition, Dzau and Re [10] suggested that studies of the RAS after binephrectomy are not conclusive, since measurements were performed acutely after nephrecto my. Indeed, Trolliet and Phillips [26] detected plasma Ang II again after 5 days of dialysis after bilateral nephrectomy, thus indicating a synthesis of renin local ized in other organs than the kidney. In the adrenal, for example, the local renin activity even increases after binephrectomy [27], Dzau and Re [10] also have chal lenged the role of renin as the main limiting factor for Ang II synthesis.…”

Section: Reninmentioning

confidence: 99%

Local Renin-Angiotensin Systems in Cardiovascular Tissues: Localization and Functional Role

Stock¹,

Liefeldt²,

Paul³

et al. 1995

Cardiology

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In its classical definition, the renin-angiotensin system (RAS) acts predominantly by endocrine mechanisms. This view has been modified since several components of the RAS and their mRNAs were found in peripheral tissues. These findings gave rise to the concept of local tissue renin-angiotensin systems. Although no cells of cardiovascular organs containing a complete RAS have been identified as of this writing, angiotensinogen and angiotensin-con-verting enzyme (ACE) are most likely synthesized within the vasculature for example. Local synthesis of renin may be limited to very small amounts, but uptake of renin from the circulation is very likely. The function of local RASs is shown by reduction of blood pressure by ACE inhibitors, which correlates better with the inhibition of ACE activity in certain tissues than with its activity in the plasma. Further studies have put forward the notion that the circulating RAS could mainly be important for acute hemodynamic stability, whereas the tissue RAS could be involved in more long term maintenance of hemodynamics. This review will try to summarize the findings leading to the concept of a local tissue renin-angiotensin system, and discuss interactions between the circulating and the local RAS in the light of recent experimental findings.

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The effect of chronic bilateral nephrectomy on plasma and brain angiotensin

Cited by 27 publications

References 0 publications

Angiotensin II type 1 receptor expression in human breast tissues

Angiotensin II type 1 receptor expression in human breast tissues

Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats

Local Renin-Angiotensin Systems in Cardiovascular Tissues: Localization and Functional Role

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