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

Plasma and serum of healthy subjects apparently contain a precursor form of renin, or 'prorenin,' which can be activated by the ice-cold temperature at which samples are customarily handled for prolonged periods in laboratories and blood banks. The effect of such prior cryoactivation for 9 days at 4 degrees C is to increase subsequent plasma renin activity (PRA) at 37 degrees C by 108 +/- 16.3% (mean +/- SE) over the nonactivated control value (P less than 0.001). At a lower temperature (-4 degrees C), the cryoactivation effect is considerably greater than at 4 degrees C. Cryoactivation is not obliterated by the prefreezing of plasma, or reduced by inclusion of bacteriostats. Nor is it attributable to any detectable reduction in angiotensinase activity. In rats, cryoactivation at 4 degrees C is much lower than in humans, suggesting a marked species difference either in prorenin concentration or in the rapidity of its spontaneous conversion after blood collection. Trypsin at near optimal concentrations also consistently activates human plasma prorenin, whether at 4, 23, or 37 degrees C indicating that cold is not an essential concomitant of tryptic activation. In excess, the magnitude of which varies among individuals, trypsin at first produces activation and later a decline in PRA, probably due to degradation of the reactants (prorenin, renin, angiotensinogen) and of the initial product (angiotensin I). The identity of angiotensin I in activated and control plasmas can be established by specific radioimmunoassay, and bioassay. Our data indicate that tryptic activation involves little direct production of angiotensin I but rather converts prorenin, thereby enhancing the angiotensin generating capacity of the plasma renin system itself. Tryptic activation in plasma of anaesthetized dogs is lower than in humans, but higher than in conscious or anaesthetized rabbits in whom the effect appears to be slight. In anaesthetized rats there is virtually no tryptic activation, which is in line with the results by cryoactivation. Since the renin--angiotensin systems of dogs, rabbits, and rats have been extensively studied in experimental models of human hypertension, these observed departures from human levels of cryoactivation and tryptic activation of prorenin deserve further investigation.
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PMID:Cryoactivation and tryptic activation of blood 'prorenin' in normal man and animals. 70 20

Nonparallel effects of renin inhibitor treatment on plasma renin activity (PRA) and the plasma levels of angiotensins (ANG), as well as on blood pressure, have been observed in subjects with hypertension. This study addresses the possibility that renin inhibitors may show a high degree of plasma protein binding in vivo and that displacement of protein-bound inhibitor during the assay of PRA in vitro may lead to overestimation of renin inhibition. Indeed, with the ultrafiltration technique it was found that 96% of the novel renin inhibitor Ro 42-5892, when added to EDTA plasma, was bound to protein. The angiotensinase inhibitors phenylmethylsulfonyl fluoride (PMSF) and 8-hydroxy-quinoline sulfate (8-OHQ), which are currently used in PRA assays, caused a displacement of protein-bound inhibitor, thereby increasing its free concentration. This displacement was sufficient to explain the reduction in IC 50 of Ro 42-5892, which was seen in the PRA assay when PMSF and 8-OHQ were added to plasma. Such reductions in IC 50 were also seen with the renin inhibitors CGP 29-287, CGP 38-560A, and SR 43-845. When Ro 42-5892 was given, 1 mg/kg intravenously in 10 min, to subjects with hypertension, it appeared that plasma ANG I and II returned to baseline after 6-8 h, whereas PRA measured in the presence of PMSF and 8-OHQ was still suppressed. However, when PRA was measured without these angiotensinase inhibitors, the inhibition of PRA was parallel to the suppression of ANG I and II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonparallel effects of renin inhibitor treatment on plasma renin activity and angiotensins I and II in hypertensive subjects. An assay-related artifact. 187 15

A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, plasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions.
Hypertension
PMID:Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation. 390 15

Plasma renin activity, plasma renin substrate (angiotensinogen), angiotensin I (AI), and plasma angiotensinase activity were measured in 8 women who had first become hypertensive during a mean 3.1 years on various oral contraceptives, and in 5 normotensive women, before and after 1 cycle of pills. All were determined by radioimmunoassay. 8 or more blood pressures were taken by 2 observers and averaged. Plasma renin activity increased from mean 2.12 to 3.52 ng/ml/hr (p greater than .2) in normal women, and from 3.0 to 5.06 in hypertensives (p less than .02). The mean plasma renin substrate values for both groups together rose from 1881 ng/ml to 4245 ng/ml. Angiotensin I rose from .029 ng/ml/hr to .049 in normals, and .027 to .037 in hypertensives. Mean plasma angiotensinase activity values rose from 3.6 to 5.4% degraded per minute in normal women and varied only from 6.5 before and to 5.9 after a pill cycle in hypertensive patients. The authors suggest that development of hypertension during oral contraceptive therapy may be due to abnormal inactivation of angiotensin.
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PMID:Effect of oral contraceptive therapy on the renin-angiotensin system in normotensive and hypertensive women. 434 64

The aim of this study was to develop a method for the measurement of renin activity in small tissue samples obtained from rat brains by the micropunch technique and to investigate the activity of brain renin in spontaneously hypertensive rats. The assay satisfied sensitive and specificity requirements. Angiotensin I was generated at a pH of 6.0; complete recovery of angiotensin I and kinetic studies supported the specificity of the method. Angiotensinase and cathepsin D-like acid protease activity were measured in parallel with renin. Renin was present in all brain regions studied and decreased with the age of the animals. An increased activity of renin was measured in several nuclei of the brain stem and in the neurohypophysis of young hypertensive rats when compared with age-matched normotensive control animals. These differences disappeared in older rats. There was a dissociation between renin and cathepsin D-like acid protease activity. No correlation existed between the distribution of renin and angiotensinase activity. The increased renin activity in brain stem nuclei of spontaneously hypertensive animals is in agreement with previous findings that the brain renin-angiotensin system contributes to the maintenance of high blood pressure in these rats.
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PMID:A micromethod for the measurement of renin in brain nuclei: its application in spontaneously hypertensive rats. 628 32

From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotension II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.
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PMID:Components of the renin-angiotensin system in the cerebrospinal fluid of rats and dogs with special consideration of the origin and the fate of angiotensin II. 700 24

Both fetal and maternal blood pressure is regulated mainly by the humoral factor, vasoactive peptides such as angiotensin II and vasopressin, but not by autoregulation and the autonomic nervous system. It is known that the normal musculoelastic tissue in the vessel wall of the coiled artery, which supplies blood to the uteroplacental blood pool, is replaced by fibrinous tissue with advancing gestation. Therefore uteroplacental circulation is similar to arterio-venous shunt; it is possibly important for the homeostasis of maternal blood pressure. It is known that hypoxemia results in both the redistribution of feto-placental blood flow, the increase of blood flow in the placenta, and the increase of fetal vasoactive peptides. Since placental proteases (vasopressinase and angiotensinase) degrade vasoactive peptides, placental proteases protect the placental vessels from the vasoconstriction by vasoactive peptides and might contribute to the redistribution of feto-placental blood flow. Therefore placental proteases effect on fetal blood pressure via regulation of fetal vasoactive peptides, which regulate placental blood flow. Although human and animal pregnancy is normally associated with a refractory response to the pressor effect of exogenously infused angiotensin II, patients with pre-eclampsia as well as nonpregnant women are sensitive to angiotensin II; thin phenomenon has been studied as one of the causes of pre-eclampsia. Since the administration of placental angiotensinase was effective in lowering blood pressure in rats with hypertension induced by the infusion of angiotensin II, placental proteases are possibly involved in the refractory response to exogenously infused angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Possible role of placental proteases via degradation of vasoactive peptides in the maternal and fetal blood pressure]. 808 9

To elucidate the involvement of angiotensin in puerperal hypertension with and without preeclampsia in the course of prior pregnancy, we measured plasma angiotensin I levels and serum placental leucine aminopeptidase (P-LAP) activities in several puerperal hypertensive patients. Placental leucine aminopeptidase (P-LAP) activities of puerperal hypertensive patients with severe preeclampsia during prior pregnancy were equal to or somewhat lower levels than those in normal puerperal women after a normal pregnancy. However, their angiotensin I levels were higher than those in normal puerperal women after a normal pregnancy. In puerperal hypertensive patients with and without preeclampsia during prior pregnancy, P-LAP activities tended to show much lower levels that those in normal puerperal women, while angiotensin I levels tended to show much higher levels than those in normal puerperal women, respectively. Since serum placental leucine aminopeptidase acts as an angiotensinase via degradation of angiotensin III (A-III), our present data suggest the involvement of angiotensin in puerperal hypertension.
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PMID:Plasma angiotensin I concentration and serum placental leucine aminopeptidase (P-LAP) activities in puerperal hypertension. 823 62

Glomerular mesangial cells are known to express angiotensin II type 1 receptors and contract in response to circulating and/or locally produced angiotensin II. In addition, stimulation of mesangial cell matrix protein synthesis by elevated levels of angiotensin II is known to contribute to the development of glomerulosclerosis. Previously, we reported that mesangial cells were positively immunostained with antiserum directed against aminopeptidase A, the principal angiotensinase in the metabolism of angiotensin II. Here we demonstrate directly that aminopeptidase A is expressed in mesangial cells cultured from rat kidney. First, cultured mesangial cells had measurable aminopeptidase A enzymatic activity. Second, immunoblots for aminopeptidase A were positive for isolated glomeruli and mesangial cells, although two bands were seen for mesangial cells (approximately 138 and 144 kD), and only the larger band was seen for isolated glomeruli and kidney. Third, Northern blot hybridizations of total RNA from mesangial cells or kidney were positive and labeled similarly sized bands. Fourth, reverse transcription-polymerase chain reaction amplification of mesangial cell total RNA yielded a partial cDNA of the expected size that was confirmed by sequencing to be identical to rat kidney aminopeptidase A. These results indicate that aminopeptidase A is expressed within mesangial cells. These results further suggest that metabolism of angiotensin II by aminopeptidase A could play a protective role in minimizing the adverse effects of angiotensin II stimulation of mesangial cells.
Hypertension 1996 Mar
PMID:Expression of aminopeptidase A, an angiotensinase, in glomerular mesangial cells. 861 96

The aim of this study was to examine whether differences in placental angiotensinase A (glutamyl aminopeptidase, EC 3.4.11.7) activities occurred in hypertensive complications of pregnancy compared with uncomplicated pregnancies. Biochemical and semiquantitative histochemical methods were used and compared for their applicability. Angiotensinase A activity was detected using L-alpha glutamyl-4-methoxy-2-naphthylamide (alpha-Glu-MNA) as substrate and Fast Blue B salt for simultaneous azo-coupling in cryostat sections of placental tissue samples from 32 patients with pre-eclampsia, 11 patients with pregnancy-induced hypertension and 44 participants with uncomplicated pregnancies. The graduated intensity of reaction product in the villous trophoblast and in fetal blood vessels was evaluated semiquantitatively in a double-blind study by light microscopy (semiquantitative score method). Score levels were related to relative frequencies of hypertensive disorders (proportional odds model) and correlated to the severity of gestational hypertension (Spearman's rank correlation). After detection of enzyme activity, the same tissue samples were homogenized and used for kinetic fluorometric measurements under the same substrate and buffer conditions as in enzyme histochemistry. Enhanced villous trophoblastic angiotensinase A activity was significantly associated with an increased frequency of pre-eclampsia in pregnant women (cumulative odds ratio x 0(1) 6.37; P < 0.001) and showed significant correlations with the severity of gestational hypertensive disorders, represented by systolic (r = 0.31; P < 0.05) and diastolic (r = 0.34; P < 0.05 blood pressure and by concomitant proteinuria (r = 044; P < 0.01). Histochemical evaluation of fetal blood vessels and biochemical measurements revealed no statistically significant results. In conclusion this study demonstrates for the first time that increased villous trophoblastic angiotensinase A activity indicates an increased likelihood of the presence of pre-eclampsia and the severity of hypertensive disorders in pregnancy.
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PMID:Histochemical evaluation of placental angiotensinase A in pre-eclampsia: enzyme activity in villous trophoblast indicates an enhanced likelihood of gestational proteinuric hypertension. 873 Aug 85


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