Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart. Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule. Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.
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PMID:Distribution of angiotensinogen in diseased human hearts. 807 4

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 +/- 18% increase above basal levels, 185 +/- 18 versus 128 +/- 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY. These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.
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PMID:Increased mRNA expression of cardiac renin-angiotensin system and collagen synthesis in spontaneously hypertensive rats. 954 81

Besides the classical endocrine renin-angiotensin system (RAS), a local RAS has been described also in the brain. We attempted to clarify the existence of a local RAS in the pineal gland. Through the use of a ribonuclease protection assay, it proved possible to detect the mRNA for angiotensinogen (AOGEN), for the angiotensin receptor type 1A (AT1a) and 1B (AT1b) and for the angiotensin-converting enzyme (ACE) in pineal glands from rats. Renin mRNA, however, could not be found by this method. By in situ hybridization and immunocytochemistry, AOGEN mRNA was co-localized with the astrocyte marker glial fibrillary acidic protein. AT1b mRNA expression exceeded the expression of AT1a mRNA and was co-localized with the pinealocyte-specific tryptophan hydroxylase. Thus, in the mammalian pineal gland there is a local formation of the components of the RAS. The presence of angiotensin II receptors further substantiates a role for angiotensins and the pineal RAS in the physiology of this gland.
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PMID:Local renin-angiotensin system in the pineal gland. 955 34

The potential involvement of the brain renin-angiotensin system in the hypertension induced by subpressor doses of angiotensin II was tested by the use of newly developed transgenic rats with permanent inhibition of brain angiotensinogen synthesis [TGR(ASrAOGEN)]. Basal systolic blood pressure monitored by telemetry was significantly lower in TGR(ASrAOGEN) than in Sprague-Dawley rats (parent strain) (122.5+/-1.5 versus 128.9+/-1.9 mm Hg, respectively; P<0.05). The increase in systolic blood pressure induced by 7 days of chronic angiotensin II infusion was significantly attenuated in TGR(ASrAOGEN) in comparison with control rats (29.8+/-4.2 versus 46. 3+/-2.5 mm Hg, respectively; P<0.005). Moreover, an increase in heart/body weight ratio was evident only in Sprague-Dawley (11.1%) but not in TGR(ASrAOGEN) rats (2.8%). In contrast, mRNA levels of atrial natriuretic peptide (ANP) and collagen III in the left ventricle measured by ribonuclease protection assay were similarly increased in both TGR(ASrAOGEN) (ANP, x2.5; collagen III, x1.8) and Sprague-Dawley rats (ANP, x2.4; collagen III, x2) as a consequence of angiotensin II infusion. Thus, the expression of these genes in the left ventricle seems to be directly stimulated by angiotensin II. However, the hypertensive and hypertrophic effects of subpressor angiotensin II are at least in part mediated by the brain renin-angiotensin system.
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PMID:The brain renin-angiotensin system modulates angiotensin II-induced hypertension and cardiac hypertrophy. 1064 33

Tonins are serine proteinases mainly found in the rat submandibular gland, which are capable of generating the pressor octapeptide angiotensin II (Ang II) not only from the classical substrate angiotensin I but also from the synthetic tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, tonin expression levels were evaluated in astrocytes and brain areas of the rat. By two different techniques (ribonuclease protection assay and reverse transcription-polymerase chain reaction), we could verify the presence of tonin mRNA in astrocytes and in the thalamus of the rat brain. Sequencing of the amplified brain cDNA determined it to be identical to that found in the submandibular gland. Central microinjection of tonin produced a transient (10-20 min) elevation of blood pressure and heart rate and induced water and saline intake within the first 10 min after injection. Urinary volume and salt excretion increased within 7 h after tonin injection. These effects were partially blocked by previously administered losartan, indicating that tonin effectively induced a central Ang II formation. Our data suggest that tonin may be an alternative pathway to Ang II generation in the brain and could participate in the physiological effects exerted by Ang II such as water and saline intake and blood pressure elevation.
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PMID:Tonin expression in the rat brain and tonin-mediated central production of angiotensin II. 1204 7

The consequences of permanent alteration to the brain renin-angiotensin system (RAS) on central vasopressinergic system was studied in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)]. Levels of vasopressin (AVP) and V1a receptor mRNAs were measured by ribonuclease protection assay (RPA) and AVP by radioimmunoassay (RIA). AVP (100 pmol/50 nl) was microinjected into the nucleus tractus solitarii (NTS) of urethane-anesthetized TGR(ASrAOGEN) and Sprague-Dawley (SD) rats and the mean arterial pressure (MAP) and heart rate (HR) baroreflex induced by phenylephrine were evaluated. AVP but not its mRNA levels were significantly lower in the hypothalamus and hypophysis of TGR(ASrAOGEN) rats. Brainstem V1a mRNA levels were significantly higher in TGR(ASrAOGEN) in comparison to SD rats (5.2+/-0.4% vs. 3.3+/-0.2% of beta-actin mRNA, P<0.05). In contrast, the hypothalamic V1a mRNA levels in TGR(ASrAOGEN) were not different from those found in SD rats. AVP microinjections induced a greater decrease in MAP in TGR(ASrAOGEN) in comparison with SD rats (-19.9+/-5.2 vs. -7.5+/-0.7 mm Hg, P<0.01). The significantly higher baroreflex sensitivity observed in TGR compared to that of SD rats was normalized after AVP microinjection. The increased brainstem V1a mRNA levels and sensitivity to AVP in TGR(ASrAOGEN) rats indicates a functional upregulation of AVP receptors in the NTS. The fact that the hypothalamic V1a mRNA levels are not altered indicates that these receptors are differentially regulated in different brain regions. This study demonstrates that a permanent deficit in brain angiotensinogen synthesis can alter the functionality of central vasopressinergic system.
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PMID:Differential regulation of central vasopressin receptors in transgenic rats with low brain angiotensinogen. 1512 Apr 78

The renin-angiotensin system plays an important role in the etiology of cardiovascular diseases. Three transgenic mouse lines overexpressing rat angiotensinogen (rAOGEN) were generated. The aim of our study was to characterize the originally undescribed second transgenic line TGM(rAOGEN)102. The transgene tissue distribution and expression of brain natriuretic peptide and collagen type III were investigated by ribonuclease protection assay. Catheter measurements of blood pressure and cardiac function were performed in anesthetized mice. End-organ fibrosis was further assessed by van Gieson staining. In line TGM(rAOGEN)102, the rAOGEN transgene was mainly expressed in liver and brain but could also be detected in hearts, kidneys, and lungs. Transgenic mice developed excessive chronic hypertension compared with their wild-type littermates. The rise of blood pressure was paralleled by cardiac hypertrophy, impaired cardiac function, and increased expression of brain natriuretic peptide. Pronounced fibrosis was detected in the hearts, lungs, and kidneys of transgenic mice. Our data indicate that overexpression of rAOGEN in mice leads to excessive hypertension, cardiac hypertrophy, impaired heart function, and pronounced fibrosis. Thus, this line TGM(rAOGEN)102 provides a new model to study hypertension-mediated end-organ damage and to evaluate new antihypertensive or cardioprotective drugs.
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PMID:Excessive hypertension and end-organ damage in a transgenic mouse line carrying the rat angiotensinogen gene. 1912 38