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

The renin-angiotensin system appears to play a major role in the regulation of sodium excretion and fluid intake in a wide variety of animal species from mammals to teleosts. In mammals the system has evolved further importance in terms of blood pressure homeostasis. This hormonal system in all species appears to involve a serum protein prohormone, angiotensinogen, a proteolytic enzyme, renin, and angiotensin I, the decapeptide product of the reaction between renin and angiotensinogen. The importance of this system to the organism appears to correlate directly with the necessity to conserve sodium while an abnormality of this process may underlie the development of hypertension in man. As the starting point of the system, angiotensinogen assumes special importance as a possible index of evolutionary development. In addition, it has been known for many years that human (viz. primate) angiotensinogen differs from that found in other mammals in its inability to be a substrate for animal renins while animal angiotensinogens readily react with human renin. Thus, the enzymatic specificity appears to reside with the prohormone. The biochemical basis for this difference is unresolved due primarily to the lack of purified human angiotensinogen. In this paper we describe methods for the purification of human angiotensinogen which have direct applicability to animal angiotensinogens. Our approach utilizes ammonium sulfate precipitation, Sephadex G-150 chromatography, multiple isoelectric focusing, and concanavalin A-Sepharose affinity chromatography. With the availability of highly purified human angiotensinogen we compared the molecular weights, heterogeneity, isoelectric points, and thermal lability of hog, rabbit, and human angiotensinogen in order to define the biochemical basis of the species variation in renin reactivity...
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PMID:Human angiotensinogen. Purification partial characterization, and a comparison with animal prohormones. 1 60

Estrogenic compounds are the most important group of drugs that can induce hypertension. Studies have shown an incidence of significant hypertension amounting to less than 1% after 1 year of taking oral contraceptives and about 2% after 5 years. The ratio of the incidence of hypertension among ''takers'' to that of ''nontakers'' has been assessed at 1.8 by 1 study and 2.6 by another. Small but significant increments in systolic and diastolic pressures can be discerned during the first 2 years of treatment. Cessation of treatment has resulted in pressures returing to pretreatment levels within 3 months. In those previously normal the highest readings during oral contraceptive use were only 155/90 mm of Hg. Severe hypertension is more likely to occur in the predisposed, and malignant hypertension has been reported. Previous hypertension, toxemia of pregnancy, obesity, and nephropathy are predisposing conditions. Although progestagens, used alone, do not cause clinical hypertension the incidence of hypertension associated with an estrogen-progestogen combination was directly related to the dose of progestagen used. Weight gain is often observed in oral contraceptive users and is occasionally accompanied by edema and hypertension. There is a marked increase in the circulating level of renin substrate (angiotensinogen) which is caused by the estrogen component of the pill. The increase in renin substrate is associated with increase in plasma levels of renin activity, angiotensin 2, and aldosterone, together with a fall in plasma renin concentration. The suppression of plasma renin concentration can persist for weeks after stopping the pill. The factors responsible for hypertension are probably intrinsic and may be either neural, vascular, or renal. Patients taking oral contraceptives should have blood pressure checks at 6-month intervals, and more frequently in high risk cases. In the management of those with only mild blood pressure elevation, such patients should change to a preparation with the lowest available estrogen dosage, 30 mcg of ethinyl estradiol, or reserve the method for use during crucial periods of family planning. With moderate hypertension the oral contraceptive should be suspended for 3-6 months. If the blood pressure falls, oral contraceptives should not be resumed but another method recommended. Continuing hypertension requires further study and possibly elective sterilization. Severe hypertension requires withdrawal of the pill, urgent investigation, and treatment. Other drugs may cause hypertension. Management of these patients is outlined. Structural formulae of progesterone, norethisterone acetate, medroxyprogesterone acetate, and norgestrel are shown.
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PMID:Drug-induced hypertension: pathogenesis and management. 18 40

The presence of acetone-soluble renin inhibitors in normal plasma has been proposed to explain the variation of plasma reactivity (PRR) in samples from normotensive and hypertensive subjects. In our experience, acetone extraction decreased PRR in relation to unextracted control values, an observation which is not consistent with the circulating lipid-renin inhibitor hypothesis. Exposure to acetone at -40 degrees C for 1 minute invariably denatured some endogenous angiotensinogen. The PRR in extracted and unextracted plasma was positively correlated with the concentration of available angiotensinogen, r = 0.955 (p < 0.05), and r = 0.964 (p < 0.01), respectively, but the addition of exogenous substrate did not uniformly increase PRR in acetone-treated plasma above control values. These data argue against the use of acetone extraction to demonstrate the existence of circulating lipid-renin inhibitors. Acetone removed 14% to 25% of the normal plasma lipids and although the extract contained most of the major lipid classes, neutral lipids were the most abundant (73% by weight). The presence of acetone-soluble phospholipids appeared to increase angiotensin I formation in the partially purified renin-angiotensinogen system, but phospholipids interfered with the radioimmunoassay and resulted in an overestimation of angiotensin I. Plasma neutral lipids decreased in vitro renin activity by 13% (p < 0.025) but this degree of inhibition suggests that lipid-renin interactions may have minimal in vivo physiological significance. In contrast to previous reports, we found the correlation between PRR and endogenous angiotensinogen in normotensive and hypertensive plasmas to be statistically significant (r = 0.643, p < 0.01). Inactivated human angiotensinogen was also shown to be an inhibitor of renin in vitro. This effect could have possibly influenced PRR values that were determined by others in the presence of inactivated angiotensinogen.
Hypertension
PMID:Evidence against acetone-soluble renin inhibitors in normal human plasma. 39 42

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

The vasopressor response to angiotensin II was found useful in the differential diagnosis of arterial hypertension and for a better understanding of its pathogenesis. Sodium supply was proved to influence significantly the pressor response to angiotensin II and not that to noradrenaline thus implying the presence of arterial receptors which bind angiotensin specifically. Angiotensin caused an increase of the urinary excretion of electrolytes in hypertensive patients and a decreased electrolyte excretion in normotensives. In most hypertensive patients angiotensin was found to decrease the plasma angiotensinogen and to activate the bradykinin-bradykininogen and fibrinolytic systems. In the presence of urinary infection angiotensin increased the platelet adhesiveness and the thrombelastographic changes proved that in this condition angiotensin increases the tendency to thrombosis.
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PMID:Angiotensin II. Vascular reactivity and humoral effects. 102 54

To investigate the possible role of vascular angiotensin converting enzyme (ACE) in the development and maintenance of hypertension, we examined aortic ACE messenger RNA (mRNA) levels in two-kidney, one clip (2K1C) hypertensive rats. The blood pressure was increased remarkably at 4 weeks (early stage) after clipping and remained elevated at 12 weeks (chronic stage). The aorta ACE mRNA levels were significantly elevated in both early and chronic stages concurrently with the increases in aortic ACE activity and blood pressure. The plasma renin activity rose markedly at 4 weeks, but returned to the normal level at 12 weeks. Neither ACE activity in the lung and plasma, nor ACE mRNA level in the lung was altered at either stage. The aorta and liver angiotensinogen mRNA levels and renal renin mRNA level were increased at 4 weeks but decreased at 12 weeks. These results indicate that the acceleration of all components in the renin-angiotensin system may contribute to the development of 2K1C hypertension in the early stage. In the chronic stage, the increased vascular ACE induced by the elevated ACE mRNA levels in the aorta may play the primary role in the acceleration of local angiotensin II formation and thus may sustain the hypertension.
Hypertension 1992 Aug
PMID:Increase of angiotensin converting enzyme gene expression in the hypertensive aorta. 132 65

1. Chymotrypsin (Cht) administration (14 mg/kg, i.v.) to rats always caused hypertension; hypotension preceded this effect in 64% of the observations (n = 11). 2. A 68% reduction of circulating kininogen but not of angiotensinogen was observed after Cht administration. 3. Cht effects were not affected by captopril, [Sar1-Leu8]-angiotensin II and alpha-adrenoceptor antagonists. In 70% of the observations (n = 10) hypotension was abolished by a mixture of histamine H1- and H2-antagonists. Therefore histamine release may explain hypotension. 4. Cht released in vitro from rat plasma, a substance producing hypertension in the rat and contraction of the guinea-pig ileum. Both effects were antagonized by [Sar1-Leu8]-angiotensin II. 5. In spite of this angiotensin release in vitro, the hypertensive component of the in vivo response to Cht seems to be due to some other substance.
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PMID:Effect of chymotrypsin on rat blood pressure. 135 73

Essential hypertension is a common human disease believed to result from the interplay of multiple genetic and environmental determinants. In genetic studies of two large panels of hypertensive sibships from widely separated geographical areas, we obtained evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension, demonstrated association of AGT molecular variants with the disease, and found significant differences in plasma concentrations of angiotensinogen among hypertensive subjects with different AGT genotypes. The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans.
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PMID:Molecular basis of human hypertension: role of angiotensinogen. 139 29

To determine whether expression of the renin-angiotensin system (RAS) is influenced by the degree of renal ablation, male Sprague-Dawley rats underwent uninephrectomy, 1 1/3 nephrectomy, or sham operation. Renin and angiotensinogen messenger RNA (mRNA) were not different among the three groups 2 weeks after surgery. The time course of expression of renin mRNA after 1 1/3 nephrectomy showed no difference versus controls at 2 and 4 weeks and a decrease at 6 weeks after surgical ablation. Because nephrons adjacent to the infarcted area in the 1 1/3 nephrectomy may be hypoperfused and a source of increased renin synthesis, intrarenal distribution of tissue renin content, renin mRNA, and immunostainable renin were examined in separate groups of rats subjected to 1 1/3 nephrectomy. The kidney was divided into two pieces, one containing the scar and scar-adjacent tissue and the other portion the tissue distant from the scar. Tissue renin content, renin mRNA, and immunostainable renin were significantly greater in the scar-adjacent tissue compared with the nonscar tissue. Immunoreactive renin was seen in the juxtaglomerular apparatuses as well as in vascular elements proximal to the juxtaglomerular apparatus and within mesangial cells of some glomeruli of the scar-adjacent tissue. In conclusion, immunostainable renin, tissue renin content, and renin mRNA were increased in scar-adjacent tissue after 1 1/3 nephrectomy. We speculate that this unique scar-associated redistribution of renin may play a pathophysiological role in the progression of renal disease.
Hypertension 1992 Oct
PMID:Renin expression in renal ablation. 139 83

Transgenic mice were generated by injecting the entire rat angiotensinogen gene into the germline of NMRI mice. The resulting transgenic animals were characterized with respect to hemodynamics, parameters of the renin angiotension system, and expression of the transgene. The transgenic line TGM(rAOGEN)123 developed hypertension with a mean arterial blood pressure of 158 mmHg in males and 132 mmHg in females. In contrast, the transgenic line TGM(rAOGEN)92 was not hypertensive. Rat angiotensinogen was detectable only in plasma of animals of line 123. Total plasma angiotensinogen and plasma angiotensin II concentrations were about three times as high as those of negative control mice. In TGM(rAOGEN)123 the transgene was highly expressed in liver and brain. Transcripts were also detected in heart, kidney and testis. In TGM(rAOGEN)92 the brain was the main expressing organ. In situ hybridization revealed an mRNA distribution in the brain of TGM(rAOGEN)123 similar to the one in rat. In TGM(rAOGEN)92 the expression pattern in the brain was aberrant. These data indicate that overexpression of the angiotensinogen gene in liver and brain leads to the development of hypertension in transgenic mice. The TGM(rAOGEN)123 constitutes a high angiotensin II type of hypertension and may provide a new experimental animal model to study the kinetics and function of the renin angiotensin system.
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PMID:High blood pressure in transgenic mice carrying the rat angiotensinogen gene. 154 85


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