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

A 15-year-old girl with hypertension, markedly elevated plasma renin activity, and normal aortogram had a well encapsulated tumor nodule removed from the right kidney. Following surgery, the plasma renin activity and blood pressure became normal and have remained so for the past 12 months. The tumor consisted of juxtaglomerular cells filling the interstitium between endothelium-lined vascular spaces. Electron microscopy disclosed the presence in the interior of the tumor, of unmyelinated nerve bundles with varicosities containing the small, densely cored vesicles characteristic of adrenergic nerves. Nerve terminals were in contact with the juxtaglomerular tumor cells. No basement membrane material was interposed between the nerve endings and the tumor cell; the width of the gap between the two plasma membranes was approximately 150 A. The presence of sympathetic fibers in the juxtaglomerular cell tumor underscores the close biologic relationship between the sympathetic and renin systems.
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PMID:Structure of a juxtaglomerular cell tumor: the presence of a neural component: a light and electron microscopic study. 90 83

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.
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PMID:Plasma endothelin levels in cirrhotic subjects. 138 39

Nerve fibers immunoreactive for vasoactive intestinal polypeptide (VIP) were demonstrated for the first time by the indirect immunofluorescence technique in human and monkey kidneys. VIP-immunoreactive nerve fibers showing varicosities were observed in the adventitia of arcuate arteries and their branches. The density of VIP-immunoreactive nerve fibers decreased from the juxtamedullary region to the cortex. Occasionally a VIP-immunoreactive varicose nerve fiber was observed near the vascular pole of a glomerulus, but no direct innervation of afferent or efferent arterioles in either monkey or human kidney was found. The distribution of VIP-immunoreactive nerve fibers in the monkey and human kidneys was similar to that reported in other species, with less density. The functional role of VIP in the innervation of the kidney is not known, but various suggestions have been made regarding the possible involvement of VIP on vasodilation of selective intrarenal blood vessels, renin secretion, and/or effects on tubules. While none of these questions were established at this time they would appear to be logical areas for further study.
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PMID:Vasoactive intestinal polypeptide nerve fibers in human and monkey (Macaca fascicularis and Macaca mulatta) kidneys. 190 38

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.
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PMID:[Histologic and ultrastructural forms of benign tumors of the kidney with renin secretion. Functional implications]. 635 4

Oral contrceptives (OCs), usd by over 30% of reproductive aged women in Belgium, are by far the most widely used contraceptive in that country. The various types of OCs include monophasic, biphasic, and triphasic combinations of an estrogen and a progestin, sequentials containing estrogen only for 7-14 days followed by a progestin through the 21st day; macrodose or microdose progestin only formulations, 3-month injectable progestins, and the morning after pill. Side effects of OCs are mainly due to metabolic effects on coagulation factors, the renin-angiotensin system, glucose tolerance, or the lipid profile. Users of OCs face increased risks of cholelithiases, thrombophlebitis, thromboembolism, cerebrovascular accidents, myocardial infarcts (among smokers over 35 years of age), and hepatic adenomas. The most troubling secondary effect is the excess cardiovascular morbidity and mortality show by contraceptive users, not just those who are obese, hypertensive, or who have histories of vascular pathology, but also those over 40 years of age and smokers. Lenght of use of OCs does not increase vascular risks. Epidemiologic studies demonstrate that vascular risks are reduced in lower dose formulations. Absolute contraindications to OC use include serious cardiovascular problems, severe hepatic pathology, estrogen-dependent tumors, pregnancy and undiagnosed gynecologic problems, and significant hyperlipidemia. Relative contraindications include severe headaches, cholelithiase, previous cholestasis of pregnancy, severe renal disease, fibromyomas, benign breast disease, age over 40 years, smoking, surgery anticipated within 4 weeks, infectious mononucleosis, falciform anemia, and immediate postpartum and lactation. Epilepsy, diabetes, depression, and varicose veins are not strictly speaking contraindications but require additonal surveillance. Lower dose formulations should be prescribed if possible. OC users should be followed up every 6-12 months. Among other steroidal contraceptive methods, sequential OCs and high dose progestin-only formulations are used for short-term treatment of specific conditions. Progestin-only minipills are used when an OC is desired but estrogens are contraindicated. Injectable progestins should be reserved for patients who for cultural or medical reasons can use no other type of contraceptive. Morning-after pills should not be considered a regular form of contraception. If OCs are used in adolescents, a low dose pill is indicated. Low dose OCs may be indicated for diabetics because of the danger of infection with IUDs and the lesser efficacy of barrier methods. If OCs are used in epileptics, they should be regular dosed because of the danger of drug interactions. Only low-dose formulations and progestin-only minipills should be used by women over 40.
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PMID:[The choice of oral contraception in 1984: general indications and specific cases]. 672 93

Evidence for the brain renin-angiotensin system being involved in the hypertension of the spontaneously hypertensive rat (SHR) includes central administration of angiotensin II (AII) antagonists and converting enzyme inhibitors that lower blood pressure in SHR. Using the unlabeled antibody enzyme method, we have found a significant difference in the distribution of brain angiotensin in SHR and Wistar-Kyoto controls (WKY). Six rats of each group were perfused with buffered picric acid-paraformaldehyde, and their brains sectioned at 50 and 100 mu. The sections were reacted with a 1:1000 dilution of AII antiserum for 36 hours followed by goat antirabbit immunoglobulin G and rabbit peroxidase antiperoxidase. For controls, preabsorption with AII, arginine vasopressin or preimmune serum were evaluated. The results showed over twice as many cells and fibers staining for AII-like immunoreactivity in SHR. The AII immunoreactive cell bodies were localized, in the order of their relative preponderance, in supraoptic and paraventricular nuclei of the hypothalamus, hippocampus, and cortex. The most prominent demonstration of AII-like immunoreactivity was observed in fiber profiles containing densely stained varicosities, which were present in many neuroanatomical subdivisions of the brain and brain stem including anterior and middle hypothalamus, basal ganglia, thalamus, locus coeruleus, nucleus of the solitary tract, limbic structures, and reticular formation. The increased fiber staining in the SHR was particularly evident in the frontal hypothalamic region, medial preoptic, and stria terminalis. We conclude that the results support the hypothesis of brain AII involvement in hypertension.
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PMID:Angiotensin-like immunoreactivity in the brain of the spontaneously hypertensive rat. 675 94

To investigate the effects of postural changes and upright exercise on atrial natriuretic peptide release and renin-angiotensin-aldosterone system behavior in patients with venous valvular insufficiency, plasma ANP, plasma renin activity and aldosterone were measured in 11 patients with venous disease and in 11 age-matched controls. In patients with large varicose veins and venous valvular dysfunction, standing was associated with a greater fall in circulating ANP levels (p < 0.05) and upright exercise was accompanied by a smaller rise in ANP concentrations (p < 0.05) as compared with controls. A significant (p < 0.001) inverse relationship was found between the number of venous segments with reflux and both upright and exercise plasma ANP concentrations (r = -0.91; r = -0.84, respectively). In the two groups the response of the renin-angiotensin-aldosterone system to upright position and physical stress was similar. These results suggest that a decreased atrial stretch, due to a reduced venous return, could account for the blunted ANP response to erect posture and exercise in patients with venous valvular incompetency.
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PMID:Atrial natriuretic peptide response to postural changes and upright exercise in patients with venous valvular insufficiency. 837 8

Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalapril, results in a phenotypic change of the medial cells of renal afferent arterioles from contractile smooth muscle cells to renin containing epithelioid cells. In normal animals, the density of the innervation of the juxtaglomerular renin containing epithelioid cells is much lower compared to the contractile cells. The effector tissues are known to play an important role in determining the pattern and density of their innervation. In this study, we tested the hypothesis that the density of the innervation of the afferent arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show that the density of the innervation had significantly increased and the association of the terminals with the smooth muscle cells had changed. There were significantly more varicosities around renal afferent arterioles from rabbits treated with enalapril (10 microg/kg/h) for 6 weeks (mean +/- SEM = 634 +/- 175 x 10(3)/mm2 vessel surface, cf. 329 +/- 69 x 10(3)/mm2 vessel surface in untreated rabbits, P = 0.05), with the number of neuroeffector junctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm2 vessel surface) and significantly more non-contacting varicosities (i.e. lying > 100 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.003). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enalapril treatment as hypothesised. Instead, it would appear that proliferation of the innervation had occurred, with the formation of additional varicosities but these varicosities failed to form neuromuscular junctions. This study has identified a form of neural plasticity in the kidney that has not previously been described.
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PMID:Extended angiotensin converting enzyme inhibition changes the innervation of renal glomerular afferent arterioles. 1058 Feb 93

Chronic inhibition of the angiotensin I converting enzyme (ACE) with enalapril, results in a phenotypic change of the medial cells of renal afferent arterioles from contractile smooth muscle cells to renin containing epithelioid cells. In normal animals, the density of the innervation of the juxtaglomerular renin containing epithelioid cells is much lower compared to the contractile cells. The effector tissues are known to play an important role in determining the pattern and density of their innervation. In this study, we tested the hypothesis that the density of the innervation of the afferent arteriole smooth muscle cells decreases when they change their phenotype from contractile to renin containing epithelioid cells. The results show that the density of the innervation had significantly increased and the association of the terminals with the smooth muscle cells had changed. There were significantly more varicosities around renal afferent arterioles from rabbits treated with enalapril (10 microg/kg/h) for 6 weeks (mean +/- SEM = 634 +/- 175 x 10(3)/mm2 vessel surface, cf. 329 +/- 69 x 10(3)/mm2 vessel surface in untreated rabbits, P = 0.05), with the number of neuroeffector junctions remaining the same (124 +/- 14 and 164 +/- 32 x 10(3)/mm2 vessel surface) and significantly more non-contacting varicosities (i.e. lying > 100 nm from the medial cells) (74 +/- 5% and 25 +/- 7%, respectively; P = 0.003). Thus, there was no reduction in the innervation of afferent arterioles in which the smooth muscle cells had changed phenotype in response to enalapril treatment as hypothesised. Instead, it would appear that proliferation of the innervation had occurred, with the formation of additional varicosities but these varicosities failed to form neuromuscular junctions. This study has identified a form of neural plasticity in the kidney that has not previously been described.
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PMID:Extended angiotensin converting enzyme inhibition changes the innervation of renal glomerular afferent arterioles. 1113 Sep 55

Treatment with beta-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N + P) and 49 received nadolol plus spironolactone 100 mg/d (N + S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 +/- 16 months. However, analyzing both complications together, the incidence was significantly higher in the N + P group than in the N + S group (39% vs. 20%; P <.04). Clinical ascites was also higher in patients in the N + P group than in the N + S group (21% vs. 6%; P <.04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N + S group (P <.01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications.
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PMID:Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study. 1254 Jul 86


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