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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes.
Hypertension 1992 Aug
PMID:Tissue renin-angiotensin systems in renal hypertension. 163 57

The expression of renin and angiotensinogen genes and their proteins were studied during the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p less than 0.0001, 2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (p = 0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r = 0.99, p = 0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2- and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene.
Hypertension 1992 Jan
PMID:Renin and angiotensinogen expression during the evolution of diabetes. 173 Apr 42

Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Nonprostanoid endothelium-derived factors inhibit renin release. 173 97

Renin-like activity can be demonstrated in arterial extracts from normal rats and from rats with Goldblatt hypertension. We have found no evidence, however, for elevated arterial renin levels in relation to plasma renin activity. Studies of the reversal of renovascular hypertension indicate that the fall in blood pressure produced by renal artery deconstriction is not renin-dependent. However, molecular biological techniques indicate that extrarenal renin gene expression is altered in some tissues, such as the adrenal gland in Goldblatt hypertension, and it is possible therefore that extrarenal renin synthesis is important in blood pressure control. This has to be distinguished from renin derived from plasma uptake.
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PMID:The role of extrarenal renin in Goldblatt hypertension. 174 94

This article describes investigations of several aspects of the molecular biology of the human renin gene and the three-dimensional structure of renin and its precursor, prorenin. Because of the importance of the RAS in hypertension, heart failure, renal failure, and possibly other disorders such as atherosclerosis, it is critical to understand the detailed control of this system. This control involves regulation at the transcriptional level, folding of prorenin, sorting of prorenin to a regulated pathway where it is proteolytically cleaved to renin and released in response to secretogogues, constitutive release of uncleaved prorenin, and nonproteolytic activation of prorenin. Currently there is great interest not only in the control of renin in the kidney, the sole source of circulating renin, but also at extrarenal sites where RAS activity may regulate cardiovascular functions. The renin gene was found to be expressed significantly in the renal juxtaglomerular cells and several other cell types. Most tissue culture cells did not express the gene; exceptions were cultured SK-LMS-1 cells and cAMP-stimulated human lung fibroblasts. Cultured human uterine-placental cells expressed the human renin gene at levels higher than in other cell types assessed. Renin mRNA had the same start site in the placental cells as the kidney and was regulated by calcium ionophores and cAMP. Thus, these cells provide primary nontransformed human cells to study the homologous human promoter. Transfected renin promoters showed cell type-specific expression and cAMP responsiveness in these cells in constructs containing as few as 102 bp of 5'-flanking DNA. DNA upstream from this appears to contain an inhibitory element(s) that may have some tissue specificity in its distribution. The cAMP response is not due to cAMP induction of a transcription factor that secondarily affects the renin promoter. A novel element may be involved, since the promoter does not contain a CRE element that mediates many cAMP responses, and the cells do not appear to respond to another known cAMP-responsive transcription factor, AP-2. Studies with transfected vectors expressing a mutant cAMP-responsive protein kinase A regulatory subunit suggest that cAMP is not responsible for basal renin promoter activity in the placental cells. By contrast, cAMP induces in essence gene activation in WI26VA4 transformed human lung fibroblasts in which renin mRNA levels increase by up to 150-fold in response to forskolin. Thus, cAMP may activate renin gene expression under certain circumstances and tissue-specific renin gene expression may be directed by more than one mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular biology of human renin and its gene. 174 21

To investigate the mechanism of maintaining hypertension in chronic two-kidney, one-clip (2K1C) rats, we studied the expression of the kidney renin gene. Total cellular RNA was extracted by the guanidine thiocyanate--CsCl method. Kidney renin messenger RNA was quantified by densitometric Northern blot analysis using 32P-labeled rat renin genomic DNA as a hybridization probe. Sixteen weeks after clipping, plasma renin concentration and plasma angiotensin II concentration did not differ between 2K1C and sham-operated rats (plasma renin activity, sham rats 16.2 +/- 4.2 vs. 2K1C rats 8.9 +/- 1.3 ng angiotensin I.mL-1.h-1; plasma angiotensin II, sham rats 14.7 +/- 7.5 vs. 2K1C rats 6.8 +/- 1.3 pg/mL), while plasma angiotensin concentration in 2K1C rats was higher than that of sham rats (p less than 0.05). Renin gene expression in the ischemic kidney was 2.2 times higher than that in the kidney of sham-operated rats (p less than 0.05), and decreased to 80% of those in the kidneys of sham-operated rats. These results suggest that overexpression of the kidney renin gene in the chronic phases of 2K1C rats may contribute to the sustained high blood pressure, and the kidney renin gene may be inhibited by posttranscriptional factors, i.e., suppressed activation of prorenin to renin.
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PMID:Consistent activation of prorenin mRNA in renal hypertensive rats. 175 39

The authors evaluated the assay performances and clinical usefulness of a newly developed solid phase radioimmunoassay (RIA) for total renin concentration (TRC) in human plasma. The direct total renin RIA was performed by a sandwich technique with a pair of anti-human renin monoclonal antibodies. Renin activation with trypsin did not change TRC. The RIA showed satisfactory assay performances and demonstrated full compatibility with a direct RIA-kit for active renin concentration (ARC) in human plasma. The values of TRC were 105.3 +/- 8.6 pg/mL in normal subjects and 136.5 +/- 14.6 pg/mL in patients with essential hypertension. The values of TRC and the ratios of ARC to TRC were high in patients with renovascular hypertension and were low in patients with primary aldosteronism. Although the TRC value in diabetic patients was 134.4 +/- 14.8 pg/mL, the ratio of ARC to TRC was low. The RIA procedure was simple since prior purification or activation of renin was not required. These results suggest that the total renin RIA and its combined use with the active renin RIA may be helpful in understanding the renin-angiotensin system in human plasma.
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PMID:Measurement of plasma total renin by the anti-human renin monoclonal antibodies. 177 17

In Wistar male rats, hypertension was induced by five-sixth nephrectomy (5/6N). Body weight, systolic blood pressure (SBP) and plasma renin concentration (PRC) were followed for 12 weeks after 5/6N. Three-dimensional reconstruction and morphometry of the JGA were carried out using a computer program "GLOM". Immunohistochemistry and electron microscopy of the JGA were also investigated. A statistically significant increase in SBP was shown after 5/6N. However, PRC showed no increase and was not correlated with SBP. Renin-containing cells were demonstrated in the afferent and efferent arterioles and the interlobular arteries. Electron microscopy revealed granules of various shapes, sizes and electron densities within the JG cell. The frequency of granulated cells in the efferent arteriole was less than that in the afferent arteriole. The afferent arteriole wall volume of 5/6N rats was significantly increased and positively correlated with SBP. The lack of relationship between PRC and SBP in this model suggests that mechanisms other than the renin-angiotensin system may be involved in the pathogenesis of hypertension.
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PMID:Three-dimensional reconstruction of juxtaglomerular apparatus (JGA) in five-sixth nephrectomized rats. 177 50

A 54-year-old woman was referred to our hospital for the treatment of a tumor of the right chest wall. Clinical examination revealed hypertension, hypokalemia, metabolic alkalosis, hyperaldosteronism and hyperreninemia. Computed tomography and an abdominal echogram indicated a tumor in the right phrenic area and two tumors in the retroperitoneum near the pancreas head. After the surgical resection of these tumors, the primary reninism was diminished. The pathological diagnosis of these tumors was leiomyosarcoma. Plasma active and inactive (trypsin-activated) renin activities (PRA) were 85.7 and 38.9 ng angiotensin I/ml/h, respectively. These PRA did not respond to either postural stimulation or suppression by the volume expansion. Active and inactive renin activities in a right phrenic area tumor were 208 and 32 ng angiotensin I/mg protein /h, respectively. Those of an abdominal tumor were 196 and 30 ng angiotensin I/mg protein/h, respectively. Renin mRNA identical in molecular size to that of the human kidney was identified by northern blot analysis. This is the first case report of renin producing leiomyosarcoma derived from the lung, which is characterized by relatively lower plasma prorenin concentrations.
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PMID:A case of renin producing leiomyosarcoma originating in the lung. 182 28

The goal of the present study was to characterize the new renin inhibitor Ro 42-5892 in vitro and in vivo. In vitro, Ro 42-5892 inhibited purified human renin and human plasma renin specifically with an IC50 of 0.7 nM and 0.8 nM, respectively. In vivo, Ro 42-5892 reduced mean arterial blood pressure in sodium-depleted marmosets and squirrel monkeys with as low a dose as 0.1 mg/kg orally. Higher doses reduced pressure by 30-35 mm Hg in both species. The duration of blood pressure decrease with 3 mg/kg orally was more than 24 hours. Maximal changes of plasma renin activity, immunoreactive angiotensin I, and immunoreactive angiotensin II were observed at 15 minutes. Renin was reduced by 74 +/- 31%, angiotensin I by 85 +/- 14%, angiotensin II by 89 +/- 17%, and immunoreactive active renin was increased by 70 +/- 39%. However, unlike pressure, these maximal effects were only transient with complete recovery of renin at 60 minutes under still reduced levels of angiotensin I (61 +/- 24%) and angiotensin II (71 +/- 38%) and increased concentrations of active renin (86 +/- 30%). The blood pressure lowering was due to specific renin inhibition as exemplified by the influence of the kidney, sodium status, species, or stereoselectivity. Moreover, the reduction of arterial blood pressure was similar to the action of the angiotensin converting enzyme inhibitor cilazapril and was not associated with reflex tachycardia in contrast to the pure vasodilator minoxidil. We conclude that Ro 42-5892 is a potent orally active renin inhibitor acting mainly by inhibition of renin in an extraplasmatic compartment.
Hypertension 1991 Jul
PMID:Ro 42-5892 is a potent orally active renin inhibitor in primates. 183 May 63


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