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Juxtaglomerular cell tumors are rare and benign tumors, occurring in young patients. The standard treatment is partial nephrectomy. We report the case of a young 22-year-old patient with a renin-secreting tumor diagnosed during an exploration of severe hypertension associated with hypokalemia that we treated by radiofrequency ablation., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Cardiac remodeling is a deleterious consequence of arterial hypertension. This remodeling results in cardiac transcriptomic changes induced by mechanical and hormonal factors (angiotensin II and aldosterone are the most important). The major features of cardiac remodeling are the hypertrophy of cardiomyocytes, interstitial and perivascular fibrosis, and microvascular rarefaction. Inappropriate stimulation of the renin-angiotensin-aldosterone system (RAAS) participates to the development of heart failure. The respective roles of angiotensin II and aldosterone in cardiac remodeling are poorly understood. The development of fibrosis in the heart depends of a balance between profibrotic (TGFβ, CTGF, inflammation) and antifibrotic (BNP, ANP, BMP4 and BMP7) factors. The profibrotic and proinflammatory effects of angiotensin II and aldosterone are very well demonstrated; however, their actions on antifibrotic factors expression are unknown. In order to explore this, we used RenTgKC mice overexpressing renin into the liver, leading to an increased plasma angiotensin II and thus induction of severe hypertension, and AS mice overexpressing aldosterone synthase (AS) in cardiomyocytes which have a doubled intracardiac aldosterone concentration. Male AS mice have a dysfunction of the coronary arteries relaxation without structural and functional changes of the myocardium. Mice derived from a crossing between the RenTgKC and AS strains were used in this work. It is shown that angiotensin II induces the expression of BNP and BMPs which ultimately slows the progression of myocardial fibrosis, and that aldosterone inhibits the expression of these factors and thus worsens the fibrosis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: In the absence of specific treatment, patients with renal vascular disease develop renal atrophy. This population frequently has hypertension refractory to medical treatment. The patients who may respond to revascularization or at the worst to a nephrectomy must be identified to optimize their therapeutic management., Methods: We conducted an observational retrospective study of hypertensive patients with unilateral renal atrophy (renal height < 9 cm) followed at the Lille University Hospital Center from 1998 to 2006. Hypertension, renal clearance (by scintigraphy with MAG3), and hypersecretion of renin (segmental/selective venous renin samples) were studied. We subsequently classified the patients into 3 groups. Medical treatment was optimized for all., Results: The mean follow-up period was 1.3+/-0.2 years. Eight patients were treated medically (group 1). Endovascular revascularization was used to treat the subjects for which atrophic kidney function accounted for more than 10% of their total renal function and with stenosis of the renal artery (>70%) (group 2, n=19). Those with a small nonfunctional kidney (<10% of total renal function) and hypersecretion of renin (ratio>1.5 in relation to the contralateral kidney) underwent a nephrectomy (group 3, n=8). The reduction in systolic blood pressure (SBP) was 27 mm Hg and diastolic blood pressure (DBP) 14 mm Hg for the overall study population (p < 0.001), without any significant aggravation of renal function. In group 1, the reduction in blood pressure was lower, with medical treatment alone; SBP fell by 13 mm Hg and DBP by 4mm Hg (p=ns) ; this group had the lowest initial blood pressure. In group 2, revascularization made it possible to improve SBP by 26 mm Hg and DBP by 14 mm Hg (p < 0.01) without significant impairment of renal function. Group 3 showed the most spectacular improvement in blood pressure, with SBP dropping by 40 mm Hg and DBP by 19 mm Hg (p=0.016). But it was also in this group that we observed an aggravation in the rate of glomerular filtration with a nonsignificant reduction of 12.8 mL/min, nonetheless superior to that expected according to the preoperative scintigraphy., Conclusion: The results of this work underline the importance of multidisciplinary management of patients with small ischemic kidneys. Preselection of patients in unstable clinical situations (refractory hypertension, progressive kidney failure, flash pulmonary edema) by isotopic and endocrinal renal evaluation provides a basis for deciding on treatment. The existence of a renin ratio >1.5 can identify the patients most likely to respond to nephrectomy. The reduction of renal function following nephrectomy must be considered in the discussion about treatment. The functional threshold initially defined at 10% may be lowered to 5%, to limit this postoperative reduction., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

Renin-secreting tumour is a rare, benign entity, responsible for hypertension due to secondary hyperaldosteronism. It must be treated surgically. In the light of a review of the literature, the authors report the first published case of resection of a juxtaglomerular tumour of the kidney by laparoscopic partial nephrectomy using an ultrasound scalpel.

A 29 year-old female patient developed severe arterial hypertension in the beginning of her second pregnancy. Investigations performed at 16 weeks of amenorrhea showed hypokaliemia in relation to severe hyperreninism: plasma active renin was 25 fold normal value, 94% as prorenin (prorenin representing 94% of total renin). Radiological investigations including ultrasonography and MRI disclosed an homogenous and avascular tumor in the right kidney. Its ablation confirmed renin tumor, and allowed recovery from HTA and continuation of pregnancy. This is the 75th reported case in the literature, enabling to make a new statement about diagnostic and therapeutic procedures, which are modified during pregnancy by contra-indication to X-rays and renin-angiotensin-aldosteron axis inhibitors.

We report a case of a renin secreting tumor, which is a very rare cause of secondary high blood pressure. A 22-year-old woman was hospitalised for exploration of high blood pressure (160/110 mmHg) with severe hypokaliemia (2,7 mmol/l) and secondary hyperaldosteronism. Physical examination was normal except the high blood pressure. Bioassays show increased kaliuresis (66 mmol/24h), plasma renin (89 pg/ml in clinostastism--108 pg/ml in orthostatism), pro-renin (1207 pg/ml in clinostastism--1412 pg/ml in orthostatism) and aldosterone (210 pg/ml in clinostastism--566 pg/ml in orthostatism). The rest of the endocrine tests were normal (cortisol and ACTH at 8:00 am, urinary free cortisol, overnight 1 mg dexamethasone suppression test). Doppler ultrasound method, performed by an experienced radiologist, did not show renal artery stenosis. Abdominal computerized tomography showed a nodular formation at the upper pole of the right kidney, isodense to renal medullary. The size tumor was 15 mm. The renal vein sampling shows high values of renin on both sides whereas, for the pro-renin, the values were higher on the tumor side. In spite of treatment with CEI (Converting Enzyme Inhibitors) and calcium antagonists, the blood pressure was not controlled. Hypokaliemia persisted (3 mmol/l) in spite of high daily potassium intake (64 mmol/l of potassium chloride). After tumor resection, reninoma was diagnosed by the pathology examination and blood pressure, plasma rennin, plasma aldosterone level returned to normal.

Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.

Hypokalaemic hypertension or resistant hypertension justify investigation for primary hyperaldosteronism. The first step of this investigation is to exclude the ingestion of liquorice, alkalis and diuretics. The second is to make sure that the treatment is compatible with the hormonal tests and that the natriuresis and kaliuresis are normal. The diagnosis then depends on an increased plasma or urinary concentration of aldosterone with a low plasma renin activity. The adenoma of Conn is present in 2/3 of cases and surgically curable, and should be distinguished from adrenal hyperplasia which is treatable with distal diuretics. This is a diagnosis which requires computerised tomography or, when inconclusive, demonstration of unilateral secretion of aldosterone. Adrenalectomy, usually by coelioscopy, is indicated in Conn's adenoma when the patient is young and the hypertension severe or recent. Surgical abstention is strongly advised in cases of adrenal hyperplasia.

CONSTRICTIVE ACTIVITY OF THE RAS AND DEVELOPMENT OF RENAL DISEASES: Several studies have suggested that the constitutive level of activity of the renin-angiotensin system (RAS), and especially of angiotensin converting enzyme (ACE) which plays an important role in the kidney in determining intrarenal angiotensin and kinin concentrations, is genetically determined and linked to the risk of developing several vascular diseases, including diabetic nephropathy, and to the risk of renal function deterioration in glomerular diseases of several origins., Inhibition of the Ras and Progression of Renal Diseases: Large controlled clinical trials have shown over the past years that inhibition of ACE has a beneficial effect and protects against degradation of renal function in type I diabetes with microalbuminuria and also in renal diseases of several origins., Pathophysiology: All these observations taken together suggest that activation of the RAS, which is necessary in certain circumstances to maintain glomerular filtration and tissue perfusion, can have a long-term deleterious effect on the heart, vessels, and kidneys, especially through glomerular hypertension which can lead to glomerulosclerosis. They support the use of ACE inhibitors, within the indications deduced from analyses of the large clinical trials, for protecting renal function in kidney diseases.

Prostaglandins play an important role in the regulation of renal hemodynamics and sodium excretion. Thus, the administration of non-steroidal anti-inflammatory drugs (NSAIDs) induces a renal vasoconstriction and sodium and potassium retention. In some high risk patients, this may lead to acute renal failure. The anti-inflammatory and renal effects of conventional NSAIDs are mediated by the non-selective inhibition of two cyclo-oxygenases, COX-1 and COX-2. Recently, highly selective COX-2 inhibitors have been developed such as celecoxib (Celebrex) and rofecoxib (Vioxx). These drugs were designed to preserve the analgesic and anti-inflammatory properties of NSAIDs while reducing their gastro-intestinal and renal side effects. Selective COX-2 inhibitors have indeed less gastro-intestinal side-effects. However, their renal profile is comparable to that of non-selective inhibitors as they induce a decrease in glomerular filtration rate and a sodium and potassium retention. Thus, despite the good gastro-intestinal safety profile of selective COX-2, one should be careful with the use of these agents in high risk patients as they may induce similar renal complications as non-selective NSAIDs.

We report an uncommon case of small renin secreting tumor of the kidney located in the medulla. The tumor was primarily detected by MRI and subsequently studied by spiral CT. The results and limitations of both techniques are discussed.

The renin-angiotensin system plays a major role in the regulation of blood pressure and sodium balance. Nitric oxide (NO) and endothelin (ET-1) are involved in the regulation of renin release and modulate the vasoconstrictive and fibrogenic effects of angiotensin II. the mechanisms that activate renin production are less effective when endogenous NO synthesis is inhibited. In the absence of NO, ET-1 prevents renin secretion. Angiotensin II stimulates the production of NO and ET-1 by endothelial cells. The vascular effects of angiotensin II are inhibited by NO reinforced by ET-1. The stimulation of ET-1 secretion could partly explain the long-term effects of angiotensin II on vascular remodelling.

Most proteases a receptor or a binding site that serves to concentrate the proteolytic activity on the cell surface and to mediate cellular effects. We looked for such a receptor for renin, an aspartyl protease. The binding of recombinant human renin labelled with 125I was studied on primary and immortalized human mesangial cells. The binding of renin was specific, saturable and was characterized by Kd = 0.4 nM and 8,000 sites/cell and Kd = 1 nM and 2,000 sites/cell for primary and immortalized cells, respectively. The binding did not depend on the active site of the enzyme, was not followed by internalization and degradation of renin and did not modify intracellular Ca2+. Stimulation of primary cells with 100 nM induced a significant increase of 3H thymidine incorporation but was not associated with an increase of the cell number. Furthermore, incubation of mesangial cells 24 h with 100 nM renin provoked an increase of tPA and of PAI1 in the conditioned medium. This increase was not modified neither by captopril nor by angiotensin II receptors antagonists. The tPA antigen elevation was confirmed by fibrin zymography showing an increase of tPA/PAI1 complexes. But, surprisingly, the reverse zymogram showed that PAI antigen increase was associated with decreased PAI activity which was due to PAI clivage in an inactive form. PAI clivage by renin required the presence of the cells and could not be obtained by incubating renin and recombinant human PAI alone. When primary mesangial cells were cultured in the presence of a specific inhibitor of renin active site, RO 42-5982, PAI accumulation in the conditioned medium was reduced by 50-60%, suggesting that endogenous renin plays a role in PAI synthesis and/or secretion. The binding of renin does not induce cAMP and cGMP generation. However, in the presence of renin (100 nM and 1 microM) the extent of cGMP generated by CNP (10 and 100 nM) was reduced by 50%. Preliminary results of the renin receptor purification by affinity chromatography indicate that the receptor Mr is about 57 kDa.

The effective development of human renin inhibitors meets its major obstacle in the absence of a suitable experimental rodent model and the species-specificity of human renin, exclusively cleaving its natural substrate human angiotensinogen. We have reconstructed the human renin-angiotensin system in transgenic rats over expressing the human angiotensinogen gene TGR (hAOGEN) 1623 by chronically injecting i.v. human recombinant renin. We have first established new in vitro enzyme kinetic techniques to measure the various components of the chimeric renin-angiotensin system and distinguished the two human and rat-specific pathways of generating angiotensin I by the human specific renin inhibitor Ro 42-5892 (Hoffmann-La Roche). Male heterozygous TGR had plasma levels of rat angiotensinogen of 1.2 +/- 0.2 mg Ang l/ml while the plasma levels of the transgene were 141 +/- 98 mg Ang l/ml (n = 41; not normally distributed). Transgene expression was found in the liver kidney, aorta, heart and adrenals. Four rats were infused i.v. with human recombinant renin at 50 ng/h over 9 days which chronically increased their blood pressure to > 200 mmHg while total plasma renin activity increased by a factor of 300. Rat renin disappeared form the plasma. This new model of experimental human renin-induced hypertension in rats will facilitate the screening and characterization of human renin inhibitors.

A renal artery stenosis is definitely responsible for hypertension when the correction of stenosis has resulted in the cure of hypertension. Imputability strategy consists in prior collection of indirect data allowing to predict the efficiency of surgical or angioplasty repair, leading to treatment indications. This strategy is based upon the pathophysiological link between hemodynamic abnormalities, increased renin secretion downstream the stenosis, and hypertension. Imputability methods are designed to examine the renine-dependency of hypertension, and both asymmetric renin secretion and renal hemodynamics if stenosis is unilateral. This asymmetry could be enhanced by acute converting enzyme inhibition. Imputability and screening strategies could be fruitfully associated in high risk patients.

The present experiment was undertaken to examine the relationship between plasma renin activity and the concentration of angiotensin converting enzyme (ACE) in plasma and renal brush border of Wistar Kyoto rats. Different experimental models known to have opposite effects on plasma renin activity were used: changes in salt intake, the deoxycorticosterone acetate (DOCA) and DOCA-salt models and the two-kidneys one clip (2K1C) model. Two weeks after the start of these experimental series, the rats were killed. At this time, blood pressure did not differ from control group, even in the 2K1C and DOCA-salt groups. As expected, PRAs were highest in the 2K1C and depleted salt groups and lowest in the DOCA, DOCA-salt and high salt groups. No relationship between this wide variation in PRA and change of ACE activity in both plasma and renal brush border could be observed. In the plasma, ACE activity in sodium-depleted rats was slightly decreased whereas no change occurred in the other models. In the kidney, DOCA treatment led to increased ACE activity in the brush border only if the animals were maintained on a high salt intake. DOCA or NaCl alone failed to have this effect. In the 2K1C model, the clipped kidneys exhibited increased brush border ACE activity whereas the unclipped kidneys did not show any significant variation in ACE activity, when compared to sham operated rats. In summary, on one hand these findings show that variations in ACE activity were linked neither to hypertension nor to changes in PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Inbred strains of mice, which produce high levels of submaxillary gland (SMG) renin have two renin genes, Ren 1 and Ren 2, per haploid genome, while strains with low levels of SMG renin have only the Ren 1 gene. Ren 1 codes for a glycosylated protein and Ren 2 codes for a highly homologous but unglycosylated and less thermostable protein. In order to determine if this difference in thermostability is related to the absence of glycosylation of renin-2 and/or to some amino acid difference between both renins we have compared the thermostability of renin-2 and a renin-2 mutant containing two potential N-glycosylation sites added by in vitro mutagenesis. Both mutant and wild type renins were expressed in AtT20 cells. Wild type renin was significantly less stable than the glycosylated mutant form upon heating. Moreover, the kinetics of heat inactivation of the mutant, in vitro deglycosylated form was similar to that of the wild type renin. This result indicates that glycosylation affects the thermostability of renin.

The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics.

The authors report a new case of primary renin-secreting renal carcinoma in a pregnant woman. The clinical, radiological and pathological findings mimicked an oncocytoma and the diagnosis was confirmed by immunohistochemical study.

A renin-secreting tumour has been observed in a 32-year-old female with severe hypertension known for 17 years. The excision of the tumour lead to the complete normalisation of the blood pressure. Histological examination showed that the tumour was benign, contained secretion granules at different stages of maturation, and derived from the juxta-glomerular apparatus. After reviewing the 40 cases previously reported in the literature we discuss the clinical presentation of this type of tumour and the approach to their diagnosis.

Since renin angiotensin (RA) system discovery during 1930 decade, its physiopathological importance was only recently demonstrated with the dramatic therapeutic value of angiotensin converting enzyme (ACE) inhibitors. The tissular localisation of some of its compounds progressively lead to the concept of a tissular RA system. However non consensus can be established concerning either its existence or its physiological role. The distribution of the classical components of the RA system in the cardiac and other tissues is not homogenous enough to demonstrate the existence of such a functional and coherent system. Numerous technical problems concerning dosage methodologies are encountered especially with angiotensin II determination and must rend cautious when interpreting data. Non specific actions of ACE inhibitors can explain discrepancies between their effects and the level of RA system activation. Indeed they interfere with other systems such as prostaglandins, leucotriens, bradykinins, free radicals. Different tissues such as those of the cardiovascular system directly interfere with angiotensin II production. However, mechanisms and enzymatic reactions that are involved in such a production are multiple and their respective roles remain to be determined.

The authors, on the basis of the literature and their own studies, envisage the behaviour of the renin-angiotensin system and of ADH during anesthesia. With regard to renin-angiotensin, it would seem that the changes reported in the past are due to the surgical procedure itself or result form haemodynamic changes but that no anesthetic has a direct effect upon the secretion of renin. For ADH, three concepts must be borne in mind: not only is secretion not influenced by anesthetics, but on the contrary anaesthesia decreases the "vasopressin" response to surgical stress. By contrast, the surgical procedure may induce the secretion of ADH responsible for coronary vasoconstriction. Finally, at high doses, ADH would appear to have an inverse antinatriuretic effect resulting in a sodium diuresis.

After a brief review of the biochemistry of the renin-angiotensin system (R. A. S.) components and of their pharmacological inhibitors, the authors describe the main biological effects of angiotensins. A particular emphasis is given to the synergistic effects of the sympathetic nervous system and of the R. A. S., and their major influence on the regulation of hydromineral metabolism and blood pressure. The methods developed for the study of R. A. S. are critically described. Finally, the most important clinical indications of the study of R. A. S. activity are given, and a special attention is paid to the conditions in which such a study must be developed in humans.

The renin-aldosterone system contributes to the regulation of arterial pressure and to the maintenance of sodium and potassium balance. Alterations in plasma potassium concentration have opposite and independent effects on renin secretion by the kidney and on aldosterone secretion by the adrenal gland. Renin secretion tends to be inhibited by hyperkalemia and stimulated by potassium depletion. In contrast, increases of plasma potassium directly stimulate aldosterone secretion. This effect of potassium on aldosterone serves as a protective mechanism against the development of hyperkalemia. Conversely, hypokalemia inhibits aldosterone production. Small changes in plasma potassium have a greater effect on aldosterone than on renin secretion. In patients with essential hypertension, diuretic induced alterations in serum potassium concentrations may affect both renin and aldosterone secretion. We have observed that therapy with a thiazide diuretic results in a reduction of serum potassium and a greater increase in renin activity than therapy with the potassium-retaining diuretic, spironolactone, despite comparable natriuretic responses with both drugs. Conversely spironolactone therapy is associated with a greater increase in aldosterone production. The greater effect of thiazides on renin activity and the greater effect of spironolactone on aldosterone production may be related to the thiazide induced reduction of serum potassium and the spironolactone induced increases of serum potassium.

A case of renin-secreting tumor of the left kidney in a 36 year-old man with hypertension of five years duration is reported. The antihypertensive therapy was unsuccessful. Following nephrectomy, blood pressure returned to normal values and is still normal, seven years later. There is no evidence of metastasis. The tumor was studied by electron microscopy and by immunohistochemistry. It is composed of two cellular structures normally encountered in the kidney: renin-secreting cells and cells similar to those of the cortical collecting ducts. This benign lesion might be hamartomatous.

Besides the juxtaglomerular cell tumors, tumors may be responsible for a primary hyperreninism syndrome. Strict criteria allow to assert that the tumor cells themselves are involved in ectopic renin secretion. They are as follows:--measurement of the renin in the blood and in tumoral tissue extracts with assessment of active anf inactive renin,--absence of any other cause of hyperreninism,--regression of the hyperreninism when the tumor is removed, and possibly recurrence when metastases appear,--demonstration of renin antigen in tumor cells by immuno-histochemistry and more recently detection of renin messenger RNA using in situ hybridization with human renin probe. About 40 cases of these tumors have been described. They are mainly renal tumors: nephroblastomas (29 cases), adenocarcinomas (7 cases) and other rare tumors. Among extrarenal tumors, it has been observed epithelial tumors (broncho-pulmonary cancers, ovarian, fallopian and pituitary tumors), soft tissue tumors (alveolar sarcomas. epithelioid sarcoma, hemangiopericytoma, leiomyosarcoma). It has not been demonstrated that tumor cells from pheochromocytoma could be themselves involved in renin production.

The effect of training on PRA, PA, hematocrit and weight loss was studied at rest and following an exercise performed until exhaustion. Two groups of subjects were used, the first, a group of 4 young well trained men (88.6% +/- 7.7 V02 max) and the second a group of 4 young untrained men (77.5% +/- 7 V02 max). PRA and PA displayed highly significant increases after exercise in both groups, but PRA resting values were lower in the well trained subjects (p less than 0.05). PRA values were also lower in the latter group after exercise, but the difference in this case was not significant. Further, the variation of hematocrit was less (p less than 0.05) and the weight loss greater in the well trained subjects. In an additional experiment, the same parameters were studied in four subjects submitted to a five month training programme (87% V02 max). Though resting values for PA remained unchanged after training, PRA resting values and PRA post exercise values were significantly lower. A comparison between the magnitude of weight loss and hematocrit variation showed that when untrained subjects became trained, the variation of hematocrit was smaller (p less than 0.05) while weight loss was larger (p less than 0.01). These observations could be explained in terms of the change in blood volume, and/or a decrease in sympathetic nervous activity induced by training.

The effects of dopamine (DA) on the smooth muscle fibres of the renal vascular bed are complex. They involve the postsynaptic alpha- and beta-adrenoceptors as well as the dopamine ones. On denervated kidney, in presence of alpha- and beta-blockers, intrarenal DA perfusion provokes vasodilation, increases natriuresis and stimulates renin secretion. The vasodilator effect of DA on the renal vascular bed was studied thanks to an isolated perfused rat kidney preparation which, when high concentrations of phenoxybenzamine and sotalol were present, made it possible to measure the effect of dopaminomimetics and dopaminolytics on the renal vascular resistance of a kidney previously vasoconstricted by continuous PGF2 alpha perfusion. (+)--Butaclamol and cis-flupenthixol proved to be invaluable tools to demonstrate the specificity of the dopamino-agonists response, since both shift the dose-response curve according to the criteria for competitive antagonism at doses at which their isomers are not active (fig. 2). Thus, it was possible to calculate the apparent pA2 for the various dopaminolytics and to classify them according to their affinity for the renal vascular dopamine receptors. Table 1 gives the classification. Flupenthixol, which has only a low affinity for the alpha 2-adrenoceptors, already inhibits the vasodilator effect of DA at 10(-8) M. The low stereospecificity of the enantiomers of sulpiride allows a distinction to be drawn between the "postsynaptic" vascular dopamine receptors and the presynaptic ones. The agonists of the renal vascular dopamine receptors provoked dose-dependent renal vasodilation on our preparation when phenoxybenzamine and sotalol were present and this was stereoselectively inhibited by (+)-butaclamol. Table II shows the activity of the dopaminomimetics meeting these criteria. p-Tyramine, di-propyl-m-tyramine and RU 24926 proved to have no dopaminomimetic effect. Their lack of activity seems to be attributable to the suppression of the hydroxyl in position 4. Mesenteric, splenic or cerebral artery preparations were also used to characterize the vascular dopamine receptors : tables III and IV compare the results taken from the literature. The classification obtained tallies quite well which suggests that the dopamine receptors located in the various vascular beds are identical. We compared the characteristics of the renal vascular dopamine receptor established from isolated rat kidney, with three other pharmacological models of dopamine receptor : the activation of dopamine-sensitive adenylate cyclase, the presynaptic modulation of the transmission of the sympathetic influx, and prolactin release (Table V).(ABSTRACT TRUNCATED AT 400 WORDS)

Eleven cases of hypertension secondary to a renal tumour secreting renin have been described in the literature between 1967 and 1978. We report here another case which presented with severe hypertension and a cerebro-vascular accident in a 30 year old woman. Intravenous urography and renal arteriography revealed a tumour of the upper pole of the left kidney. Measurement of renin levels in the renal veins demonstrated hypersecretion on the side of the tumour. Tumorectomy was followed by normalisation of blood pressure levels. Histopathological examination confirmed the diagnosis of a tumour of the juxta-glomerular apparatus.

Two cases of renal benign renin-secreting tumours (juxta-glomerular cells tumors) have been compared by optical and electron microscopy. The first is the simplest type of tumoral form which can be observed. This contains secretory cells similar to epitheloid cells of normal juxta-glomerular apparatus, which multiply in well developed arteriolar and capillary network. As in afferent arterioles of glomeruli, transformation of parietal smooth cells in secretory cells can be observed. This results in the presence of intermediate cells, containing both contractile filaments and secretory granules. This tumor does not contain nerves. The second tumor has a more complex structure. Beside usual secretory cells, tubular formations and adrenergic amyelinic nerves are observed. Tubes and nerves have been described separated in many juxta glomerular cells tumors but had never been observed in association. Tubules with small lumen are made of highly dystrophic cells. High concentration of "kallikrein" in tumoral tissue, strongly suggests that they proceed from distal tubule. Unmyelinated nerves from varicosities containing densely cored vesicles characteristics of adrenergic nerves, and synaptic terminal endings on secretory cells. The presence of nerve bundles suggest a nervous regulation of tumoral secretions. This hypothesis is confirmed by dynamic explorations of sympathetic system.

Renal and vascular prostaglandins, which are vasoactive factors with local action, are implicated in the regulation of arterial blood pressure and might play a role in the genesis of arterial hypertension. By their properties of supervision on intrarenal blood flow, on renin secretion, on excretion of electrolytes and on the antidiuretic action of vasopressin, the prostaglandins E2 and I2 of renal origin indirectly control the blood pressure balance. In patients suffering from essential hypertension the urinary excretion level of renal prostaglandins is normal or diminished. When given to patients in pharmacological doses, prostaglandins exert a marked hypotensive effect. Non steroidal antiinflammatory drugs who act through inhibition of the synthesis of prostaglandins combat the action on blood pressure of several antihypertensive agents and lower natriuresis normally induced by some diuretics. These data show the diversity of action of the prostaglandins. By these properties, prostaglandins take part in control mechanisms on arterial blood pressure and facilitate the therapeutic use in patients suffering from hypertension.

The association of hypercalciuria, salt losing renal disease, and a defect in urine concentrating ability with high renin and aldosterone levels is described in two brothers. One child had marked nephrocalcinosis by the age of 3 and the other severe growth retardation. In one child all the abnormalities were abolished with indomethacin which was responsible for a marked decrease in urinary. The data and the family study suggest that this condition is a proximal tubular disorder with atuosomal recessive inheritance.

During immersion in sitting position to the neck of 10 normal adult males, natriuria is significantly increased even after pretreatment with captopril (2 mg X kg-1, p.o.). Inhibition of the renin-angiotensin-aldosterone cascade does not completely block the mechanisms causing natriuria during immersion.

Benign renin secreting tumors of the kidney, of which the authors report a new case, are an uncommon cause of arterial hypertension. The lesion is unique, benign, richly vascularized and constituted by epithelioid cells similar to those seen in the normal juxta-glomerular apparatus. Noteworthy and of great diagnostic value is the massive infiltration of the tumoral tissue by mastocytes. The ultrastructural examination clearly shows the differentiation of the secretory cells from the smooth muscular fibresof the vessel walls. The other types of renin secreting tumours are briefly considered.

The decrease of sympathetic activity by the beta-blocking drug, as demonstrated by the decreased electric activity of the splanchnic nerve and by the decreased urinary catecholamine reponse to tilt as well as by the decreased levels of plasma dopamine beta-hydroxylase exists not only in hypertension with elevated PRA but also in hypertension with normal or low PRA. In these latter cases the antihypertensive effect is better explained by the decrease in the sympathetic nervous system activity than by the decrease of PRA. This effect seems to be indirect and probably, as suggested by Lewis, as a result of damping sensory input to the central nervous system from the heart, whose capacity to respond to exercice and stress is blunted by beta-adreno-receptor blockade.

Acebutolol, a new cardioselective beta-blocking agent, has been given for 5 days, at a daily dosage of 600 mg to 8 patients with mild essential hypertension. Plasma Renin Activity (PRA), Plasma aldosterone (PA), Aldosterone Metabolic Clearance Rate (AMCR), Aldosterone Secretion Rate (ASR) have been compared before and after treatment. Whatever is the daily sodium intake, acebutolol decreases PRA and does not change AMCR. Under a normal sodium diet, PA and ASR are unchanged, in spite of the fall in PRA. On the contrary, under a sodium free diet, the decrease in PRA is accompanied by a decrease in PA and ASR.

The authors studied the reproductibility of the measures of the haemodynamic (HR-SAP-DAP) and hormonal (PRA-plasma catecholamine) parameters at rest and during stress. 11 normotensive male subjects, age 20-26 years, have release 2 stress tests on ergometric bicycle spaced from 8 to 180 days (mean 54.2 days). The measure of haemodynamic parameters is reproducible during stress. The PRA measures is reproducible at stress instead of individual variations of natriuresis between 3-10 g. The measure of plasma norepinephrine levels is reproducible for strict rest and during stress. This express an identical participation of the sympathetic system for the same physical work load. This results express the interest of stress tests for the definition of a normal blood pressure and hormonal profile.