Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aminopeptidase A (APA; angiotensinase A, E.C. 3.4.11.7) can be demonstrated histochemically (by simultaneous azo coupling) in the glomerulus and JGA of the rat and mouse kidney by light and electron microscopy. In the rat JGA, the APA is localized in Goormaghtigh's cells (mainly at the cell membranes), and in the mouse it is to be found in epitheloid cells (at the cell membranes and in lysosomal structures). From quantitative histochemical investigations of subcortical glomeruli, it can be proven that the aminopeptidase A determined by histochemical means is the angiotensinase A that splits N-terminal aspartate from AI or AII. Animal experiments (sodium depletion, sodium loading, adrenalectomy) bring about marked APA alterations in the glomeruli and in the JGA. The strongest APA alterations can be seen in the adrenalectomized animals, namely an increase of the APA activity in the glomeruli and parts of the JGA. The findings suggest that this enzyme is important for the regulation of the glomerular blood flow and the renin secretion or production by means of angiotensin degradation.
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PMID:Histochemistry of angiotensinase A in the glomerulus and the juxtaglomerular apparatus. 629 Jul 47

Nonaldosterone mineralocorticoids, such as deoxycorticosterone (DOC) and 18-hydroxy-DOC, have been reported to be elevated in some patients with primary aldosteronism (PA). Since DOC is a probable precursor of a more potent mineralocorticoid, 19-nor-deoxycorticosterone (19-nor-DOC), this study evaluated urinary free (UF) 19-nor-DOC excretion in 6 patients with PA and compared the results to those from 11 patients with low renin hypertension (LRH) and 7 normotensive subjects. PA was due to either an aldosterone-producing adenoma (APA; 4 patients) or bilateral adrenal hyperplasia (2 patients) diagnosed by adrenal venous catheterization or surgery. Compared to LRH subjects, patients with PA had a higher mean blood pressure (137 +/- 9 vs. 114 +/- 3 mm Hg), a lower plasma potassium level (3.1 +/- 0.2 vs. 3.9 +/- 0.1 meq/1) and greater renin suppression (0.3 +/- 0.1 vs. 0.6 +/- 0.1 ng angiotensin I/ml . h). UF 19-nor-DOC levels were elevated in PA subjects compared to those in normotensives (3,716 +/- 1,517 vs. 428 +/- 112 ng/day) but not compared to those in LRH patients (1,237 +/- 471). Two patients with APA had distinctly elevated UF 19-nor-DOC levels (11,137 and 7,744 ng/day), but another APA patient had the lowest value (305 ng/day). UF 19-nor-DOC positively correlated with the aldosterone secretion rate in PA (r = 0.75) but not LRH subjects. In conclusion, this study demonstrates that patients with PA may have elevated levels of UF 19-nor-DOC which are proportional to the aldosterone excess and could be a contributing factor to the hypertension, hypokalamia, and excess mineralocorticoid activity of this disease.
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PMID:19-nor-deoxycorticosterone excretion in primary aldosteronism and low renin hypertension. 633 72

Spironolactone (SPL) corrects hypertension, hypokalemia, and hyporeninemia in patients with primary hyperaldosteronism (PHA) by blocking mineralocorticoid (MCH) receptors. We evaluated the effect of continuous SPL treatment (100 to 300 mg/day for 7 days to 9 years) on plasma renin (PRC), potassium, aldosterone (PA), 18-hydroxycorticosterone (18-OHB), deoxycorticosterone (DOC), and corticosterone (B) concentrations and 24-hour urinary excretion of aldosterone (UA) in 24 patients with PHA (15 with an aldosterone-producing adenoma [APA] and nine with idiopathic PHA [IHA]). Despite the normalization of PRC and K in both APA and IHA patients by SPL, UA and PA failed to increase in APA (55.8 +/- 8.8 to 51.4 +/- 7.3 micrograms/24 hr and 54.0 +/- 9.4 to 44.6 +/- 6.2 ng/dl, respectively) in contrast to rises in IHA patients (22.3 +/- 2.5 to 69.3 +/- 10.3 micrograms/24 hr and 16.0 +/- 1.0 to 49.9 +/- 9.9 ng/dl). Similar corrections with amiloride (20-40 mg/day for 2 months) in one patient with APA produced a three- to fourfold increase in UA and PA. In addition, while on SPL the characteristic fall or no change in PA and 18-OHB during upright posture persisted in all APA patients despite further increases in PRC (4.48 +/- 1.15 to 7.86 +/- 1.89) and K (4.0 +/- 0.1 to 4.3 +/- 0.1). The patterns of the aldosterone precursors, DOC, B, and 18-OHB, and their ratios to acute stimulation with cosyntropin were not altered by SPL. Thus, SPL treatment causes a sustained impairment of the aldosterone secretory response to normalized PRC and K, but not to ACTH stimulation, only in patients with APA.
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PMID:Studies of impaired aldosterone response to spironolactone-induced renin and potassium elevations in adenomatous but not hyperplastic primary aldosteronism. 636 Aug 78

Quantitative histochemical measurements of aminopeptidase A (APA, angiotensinase A) were done kinetically in the kidney glomeruli of rats after short-term experiments (treatment with furosemide as well as captopril for 2, 4, and 6 h). The APA activities increased after treatment with furosemide or captopril. Highest activities were determined after 4 h using furosemide and 6 h using captopril. It is concluded that glomerular APA activities correspond to the renin/angiotensin plasma levels and that the fast changes of APA activities are well demonstrable by kinetic densitometric measurements in situ.
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PMID:Quantitative histochemistry of the angiotensinase A (APA) in the renal glomeruli of rats after stimulation of the renin-angiotensin system. 638 Sep 95

The renin-angiotensin and cardiac natriuretic systems play an important role in the pathophysiology of congestive heart failure (CHF). The status of the membrane-bound pulmonary and renal activities of three ectoenzymes involved in the regulation of these systems-angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase A (APA)-was investigated in Wistar rats 3 months after induction of myocardial infarction (MI) and in sham-operated (control) rats. Plasma renin activity and ACE activity, plasma angiotensin II (Ang II) levels, and atrial natriuretic factor levels were simultaneously determined. The lung ACE activity was decreased in MI rats compared with control rats (P < .0001), and this decrease depended on the severity of the heart failure. In contrast, plasma ACE activity was increased in MI rats (P < .01), and this increase was also proportional to the severity of MI. Northern blot analysis showed that the lung ACE mRNA level in severe MI rats was half that of the control rats. Renal ACE activity of the MI rats was not affected, and neither renal or pulmonary NEP nor pulmonary APA activities were altered. Thus, lung ACE gene expression appears to be both organ- and enzyme-specifically regulated during CHF. Whereas plasma renin was increased in heart failure rats, plasma Ang II levels were not different from those of control rats. Thus, decreased lung ACE activity could possibly contribute to keeping plasma Ang II levels in the normal range. The decrease in lung ACE activity and mRNA levels, combined with increased plasma ACE activity, represents a novel aspect of endothelial dysfunction in CHF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Discrepancy between plasma and lung angiotensin-converting enzyme activity in experimental congestive heart failure. A novel aspect of endothelium dysfunction. 806 19

Although aldosterone (Aldo.) secretion is regulated by various humoral factors, evidence has accumulated to support an involvement of dopaminergic system in its regulation. The pathophysiological significance of the dopaminergic system in primary aldosteronism (PA) however remains unknown. In the present study, we examined the effects of metoclopramide (MCP) on Aldo. secretion in normal subjects (n = 11) and patients with essential hypertension (EH, n = 8), aldosterone-producing adenoma (APA, n = 10), and idiopathic hyperaldosteronism (IHA, n = 6). Plasma Aldo., prolactin (PRL), renin, cortisol, serum sodium, and serum potassium levels were determined before and 30 min after i.v. bolus injection of 10 mg MCP at 9 a.m. Plasma Aldo. showed a significant increase after MCP in normal subjects, EH, and APA, but not in IHA. The incremental response of plasma Aldo. was largest in APA and smallest in IHA. The percentage increase in plasma Aldo. from the basal level was significantly attenuated in IHA, while no significant difference was seen among other groups. Although plasma PRL showed a significant increase in response to MCP, no difference of the change was seen among the groups. There was no significant change in plasma cortisol, renin, serum sodium, and serum potassium levels in response to MCP. In addition, the response of Aldo. to MCP was normalized in APA after unilateral adrenalectomy, while that of PRL did not change. These results indicate that the adrenal dopaminergic activity is enhanced in APA and attenuated in IHA and suggest an involvement of the dopaminergic system in the pathogenesis of IHA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopaminergic regulation of aldosterone secretion: its pathophysiologic significance in subsets of primary aldosteronism. 852 76

1. Angiotensin-responsive aldosterone-producing adenomas (AII-R-APA) have increased expression of renin mRNA compared with angiotensin-unresponsive aldosterone-producing adenomas (AII-U-APA) or normal adrenals. 2. Further, significant associations between the BglI, TaqI and HinfI RFLP and aldosterone responsiveness to the renin-angiotensin system of the two subgroups of patients have been reported. 3. Using the polymerase chain reaction based technique single stranded conformational polymorphism, we detected no alterations in exon 1 of the renin gene in peripheral blood leucocyte DNA from normal AII-U-APA and AII-R-APA subjects. 4. Using long-PCR, we amplified a fragment of the renin gene consisting of a region covering 500 bp upstream of exon 1, exon 1 and intron A. No gross changes in this area of the renin gene were found in the three groups of subjects studied. However this does not exclude small alterations in this area.
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PMID:Analysis of the renin gene in patients with aldosterone-producing adenomas by polymerase chain reaction-single stranded conformational polymorphisms and long polymerase chain reaction. 858 11

Angiotensin (Ang) II and Ang III are two peptide effectors of the brain renin-angiotensin system that participate in the control of blood pressure and increase water consumption and vasopressin release. In an attempt to delineate the respective roles of these peptides in the regulation of vasopressin secretion, their metabolic pathways and their effects on vasopressin release were identified in vivo. For this purpose, we used recently developed selective inhibitors of aminopeptidase A (APA) and aminopeptidase N (APN), two enzymes that are believed to be responsible for the N-terminal cleavage of Ang II and Ang III, respectively. Mice received [3H]Ang II intracerebroventricularly (i.c.v.) in the presence or absence of the APN inhibitor, EC33 (3-amino-4-thio-butyl sulfonate) of the APN inhibitor, EC27 (2-amino-pentan-1,5-dithiol). [3H]Ang II and [3H]Ang III levels were evaluated from hypothalamus homogenates by HPLC. EC33 increased the half-life of [3H]Ang II 2.6-fold and completely blocked the formation of [3H]Ang III, whereas EC27 increased the half-life of [3H]Ang III 2.3-fold. In addition, the effects of EC33 and EC27 on Ang-induced vasopressin release were studied in mice. Ang II was injected i.c.v. in the presence or absence of EC33, and plasma vasopressin levels were estimated by RIA. While vasopressin levels were increased 2-fold by Ang II (5 ng), EC33 inhibited Ang II-induced vasopressin release in a dose-dependent manner. In contrast, EC27 injected alone increased in a dose-dependent manner vasopressin levels. The EC27-induced vasopressin release was completely blocked by the coadministration of the Ang receptor antagonist (Sar1-Ala8) Ang II. These results demonstrate for the first time that (i) APA and APN are involved in vivo in the metabolism of brain Ang II and Ang III, respectively, and that (ii) the action of Ang II on vasopressin release depends upon the prior conversion of Ang II to Ang III. This shows that Ang III behaves as one of the main effector peptides of the brain renin-angiotensin system in the control of vasopressin release.
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PMID:Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release. 887 46

The hydrolase aminopeptidase A is an important regulator of the renin-angiotensin system, since it inactivates its most vasoactive component angiotensin II (Ang II). A single i.v. injection of a monoclonal antibody against mouse aminopeptidase A (ASD-4) induces a membranous-like glomerulonephritis in mice, characterized by an acute albuminuria, that is not dependent on complement, the coagulation system, or inflammatory cells. We hypothesized that this albuminuria is the consequence of a reduction in aminopeptidase A enzyme activity, that might subsequently lead to an increase in Ang II levels. Aminopeptidase A enzyme activity was analysed in vitro by a fluorimetric enzyme assay and in vivo by enzyme histochemistry. The role of Ang II in the induction of albuminuria in this model was studied by measuring the renal aminopeptidase A mRNA expression in our model by a competitive PCR assay as an indirect measure of Ang II levels. In addition, the role of Ang II in this model was studied by preventing the formation of Ang II with the angiotensin-converting enzyme inhibitor enalapril or by blocking of the Ang II receptor with the AT1 receptor antagonist losartan. Only antibodies that were able to inhibit the aminopeptidase A enzyme activity in vitro and in vivo induced an acute albuminuria in mice. Renal aminopeptidase A mRNA expression was increased by injection of the anti-aminopeptidase A antibody. Both enalapril and losartan treatment reduced the acute albuminuria, measured 1 day after injection of a monoclonal antibody against aminopeptidase A, by 91% and 83%, respectively. It is concluded that the induction of acute albuminuria is correlated to the enzyme-inhibiting capacity of the anti-aminopeptidase A antibodies. This impaired enzymatic activity most likely leads to an increase in the levels of Ang II, the best known substrate of aminopeptidase A. The results of our additional experiments are in keeping with our hypothesis that Ang II mediates this acute albuminuria. Whether this occurs by an increase of blood pressure or by a growth factor-like effect remains to be defined by further studies in this model.
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PMID:Inhibition of aminopeptidase A activity causes an acute albuminuria in mice: an angiotensin II-mediated effect? 894 74

Angiotensin (Ang) II is not the only active peptide of the renin-angiotensin system. Several of its degradation products including Ang III (obtained by deletion of the N terminal amino acid), Ang IV (obtained by deletion of the two N terminal amino acids) and Ang II(1-7) (obtained by deletion of the C terminal amino acid) also possess biological functions. These peptides are formed via the activity of several enzymes, aminopeptidase A for Ang III, aminopeptidases A and N for Ang IV, prolylendopeptidase and carboxypeptidases for Ang II(1-7). Ang III possesses most of the properties of Ang II and shares the same receptors. This peptide is particularly important in brain and pituitary physiology and plays a major role in the secretion of arginine vasopressin. Ang IV possesses its own receptors distinct from AT1 and AT2. Some of its effects (for example, stimulation of the synthesis of the type 1 inhibitor of plasminogen activator by endothelial cells) were previously attributed to Ang II. Others are opposed to Ang II effects (renal and cerebral vasodilation). Its role in vascular, renal and cerebral physiology remains to be determined. Ang II(1-7) exhibits direct and indirect effects, the latter resulting from Ang II(1-7)-dependent formation of nitric oxide and vasodilatory prostaglandins. Ang II(1-7) recognizes both specific receptors and AT1 receptors as shown by the partial antagonistic properties of losartan. Ang II(1-7) plays essentially a role in the control of the hydroelectrolytic balance by increasing glomerular filtration rate, urinary output and sodium excretion rate.
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PMID:Active fragments of angiotensin II: enzymatic pathways of synthesis and biological effects. 905 51


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