Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcatheter arterial infusion chemotherapy is one of the most useful therapeutic procedures for gynecologic malignancies. Recently, several reports have been published about Angiotensin II-induced hypertension chemotherapy and the efficacy of the method, but there have been no reports to evaluate an application for gynecologic malignancies. We evaluate the usefulness of the method for gynecologic malignancies demonstrating the changes of hemodynamics of the tumor using 81mKr scintigraphy. Thirteen patients with pathologically confirmed gynecologic malignancies were evaluated by angiography and continuous infusion of 81mKr via the catheter with and without Angiotensin II. At first, continuous infusion of 81mKr was performed under the superselective catheterization of the uterine artery. The radioactivities in the ROI were counted. Then, withdrew the catheter from the uterine artery to the internal iliac artery, and again continuously infused 81mKr and counted the radioactivities in the same ROI. Finally, keeping the catheter in the internal iliac artery, Angiotensin II and 81mKr were infused simultaneously. And counted the radioactivities. The radioactivities were highest when the catheter tip was placed in uterine arteries and lowest when the catheter tip was placed in internal iliac arteries. But radioactivities in the ROIs were definitely increased when Angiotensin II was used, even if the catheter tip was keeping in the internal iliac arteries. The optimal catheter position of transcatheter arterial chemotherapy for gynecologic malignancies is at proximal uterine artery. Since Angiotensin II-induced hypertension may increase blood flow of tumors, it seems to have indication for post-operative cases, highly advanced cases and cases with difficulties to perform superselective catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[81mKr scintigraphic evaluation of hemodynamics in gynecologic malignancies under condition of angiotensin II-induced hypertension]. 143 80

TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin-angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension.
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PMID:Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats. 143 62

We have previously shown that the stimulatory effects of guanine nucleotides, N-ethylcarboxamide-adenosine and other agonists on adenylate cyclase activity were diminished in aorta and heart sarcolemma of spontaneously hypertensive rats (SHR) [Anand-Srivastava (1988) Biochem. Pharmacol. 37, 3017-3022]. In the present studies, we have examined whether the decreased response of these agonists is due to the defective GTP-binding proteins (G-proteins) which couple the receptors to adenylate cyclase, and have therefore measured the levels of G-proteins in aorta and heart from SHR and their respective Wistar-Kyoto (WKY) controls by using pertussis toxin (PT)- and cholera toxin (CT)-catalysed ADP-ribosylations and immunoblotting techniques using specific antibodies against G-proteins. The labelling with [32P]NAD+ and PT identified a 40/41 kDa protein in heart and aorta from WKY and SHR and was significantly increased in the hearts (approximately 100%) and aorta (approximately 30-40%), from SHR as compared with WKY. Immunoblotting revealed an increase in the levels of the G-protein alpha-subunits Gi alpha-2 and Gi alpha-3 in heart and Gi alpha-2 in aorta, whereas no change in Go alpha was observed in heart from SHR and WKY. On the other hand, no differences were observed in CT labelling or immunoblotting of stimulatory G-protein (Gs) in heart and aorta from WKY and SHR. In addition, CT stimulated the adenylate cyclase activity in heart sarcolemma from WKY and SHR to a similar extent. These results were correlated with adenylate cyclase inhibition and stimulation by various hormones. Angiotensin II (AII), atrial natriuretic factor (ANF) and oxotremorine-mediated inhibition was found to be greater in SHR as compared with WKY, whereas the stimulatory effects of adrenaline, isoprenaline, dopamine and forskolin were diminished in SHR aorta as compared to WKY. These results indicate that regulatory protein G(i) is more expressed in SHR, which may be associated with the decreased responsiveness of stimulatory hormones and increased sensitivity of inhibitory hormones to stimulate/inhibit adenylate cyclase activity. It may thus be suggested that the enhanced G(i) activity may be one of the mechanisms responsible for the diminished vascular tone and impaired myocardial functions in hypertension.
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PMID:Enhanced expression of inhibitory guanine nucleotide regulatory protein in spontaneously hypertensive rats. Relationship to adenylate cyclase inhibition. 144 83

The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin-angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Dec
PMID:Role of angiotensin subtype 2 receptor in neointima formation after vascular injury. 145 89

The development of orally active renin inhibitors has been plagued by limited bioavailability in animals and humans. A-74273 is a novel, potent nonpeptide inhibitor of human renin (IC50 = 3.1 nM). This compound was absorbed into the portal and systemic circulations of anesthetized rats, ferrets, monkeys, and dogs after intraduodenal dosing. This favorable pattern also was observed after oral dosing in conscious animals, except in monkeys. Hepatic extraction of A-74273 was more efficient in rats and monkeys than in dogs or ferrets. A-74273 modestly inhibits dog renin, and when given orally as the base (0, 0.3, 1, 3, 10, and 30 mg/kg; n = 8 per dose) to conscious, salt-depleted dogs it induced dose-related reductions in mean arterial pressure and plasma renin activity. Peak falls in mean arterial pressure from normotensive baselines were -14 +/- 1, -26 +/- 3, and -44 +/- 3 mm Hg for the 3, 10, and 30 mg/kg groups, respectively (p < 0.05). Baseline plasma renin activity values (10.9 +/- 1.1-12.7 +/- 1.1 ng angiotensin I/ml/hr) were maximally inhibited, ranging from 43 +/- 8% at 0.3 mg/kg to 98 +/- 1% at 30 mg/kg. Bioavailability in this model was estimated to be 54 +/- 13% when plasma drug levels were determined by a renin inhibitory activity assay, but bioavailability was lower when compared with high-performance liquid chromatographic analysis of A-74273. This discrepancy was accounted for by the identification of structurally similar metabolites that are as active as the parent drug against human renin but much less potent against dog renin.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Dec
PMID:Discovery of a well-absorbed, efficacious renin inhibitor, A-74273. 145 92

Non-modulation is a trait characterized by abnormal angiotensin-mediated control of aldosterone release and the renal blood supply. To determine whether non-modulation defines a specific subgroup of the hypertensive population and its utility as an intermediate phenotype, we have studied the distribution of this quantitative trait, whether its features are reproducible on repeated testing, and whether there is concordance of its multiple features. Essential hypertensive patients (224) and normotensive subjects (119) received an infusion of angiotensin II (Ang II) at 3 ng.kg-1.min-1 for 30-45 minutes. p-Aminohippurate (PAH) clearance was assessed as an index of renal plasma flow while the subjects were on a 200 meq sodium diet; plasma aldosterone levels were measured while the subjects were on a 10 meq sodium diet. In 54 subjects, diuretic-induced volume depletion superimposed on a low salt diet was substituted for the Ang II infusion. The results of each study were submitted to maximum likelihood analysis to assess bimodality. In response to both diuretic-induced volume depletion (p < 0.000023) and Ang II infusion (p < 0.0009), aldosterone responses were bimodally distributed in the essential hypertensive but not in the normotensive subjects, suggesting that this trait identifies a discrete subgroup. In the 59 subjects who had both an adrenal and renal study, 50 (85%) were concordant. Finally, in 27 subjects studied two to six times over a span of 1-60 months, the intraclass correlations of the adrenal, PAH, or both responses were highly significant (p values between 0.001 and 0.00007), indicating high reproducibility of results on repeated testing.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Dec
PMID:Non-modulation as an intermediate phenotype in essential hypertension. 145 94

Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It acts through at least two types of receptors termed AT1 and AT2. We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1. The human AT1 gene was mapped to chromosome 3q by polymerase chain reaction analysis of DNA from a panel of human-hamster somatic cell hybrids. The predicted amino acid sequence is 95% identical to the corresponding rat and bovine receptors and 25% and 22% identical, respectively, to the receptors encoded by the RTA and MAS genes. Characterization of several human cDNA clones demonstrated the existence of two alternate 5'-untranslated regions (UTRs) that contain a common initial sequence but differ by the presence or absence of an insertion of 84 base pairs. In the genomic sequence, the coding sequences are contained in a single exon, with an intron occurring in the 5'-UTR at the position of insertion of the 84-base pair sequence. The exons encoding the alternate 5'-UTRs are located at least 3.8 kilobases away from the exon encoding the protein. Reverse transcription-polymerase chain reaction analysis showed that both forms of 5'-UTR are present in approximately equal abundance in a range of tissues expressing AT1. The reagents developed in this work may be useful in testing the hypothesis that genetic variations in angiotensin II receptor function are associated with a tendency to develop hypertension.
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PMID:Genetic analysis of the human type-1 angiotensin II receptor. 150 24

The plasma and adrenal renin-angiotensin system in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were examined in animals at 5, 11, 18, and 25 weeks of age. Plasma active renin was significantly increased in 18- and 25-week-old SHRSP with impaired renal function, whereas there was no difference in the plasma prorenin level or renal renin content between the two strains at all ages examined. Thus, the rate of activation of prorenin seems to be enhanced in the kidney of SHRSP with malignant hypertension. Adrenal renin contents were severalfold higher in SHRSP than WKY rats at all ages. However, adrenal angiotensin peptides were not increased in SHRSP aged 5 and 11 weeks. In 18-week-old SHRSP, adrenal angiotensin II (Ang II) and III (Ang III) levels were fourfold and 1.8-fold higher, respectively, than in WKY rats, accompanied by 1.5-fold higher plasma aldosterone. Increased adrenal angiotensin and plasma aldosterone were also found in 25-week-old SHRSP. Zonal distribution studies indicated that the elevated Ang II and III in SHRSP were derived mainly from the capsular tissue (the zona glomerulosa). To examine the contribution of circulating angiotensin to the adrenal angiotensin content, effects of bilateral nephrectomy on adrenal angiotensin and renin were examined in 18-week-old rats. At 24 hours after nephrectomy, plasma angiotensin, prorenin, and active renin were decreased to almost negligible concentrations. Conversely, in both adrenal capsular and decapsular tissues of SHRSP and WKY rats, neither angiotensin nor renin was significantly decreased after nephrectomy. These results suggest that the increase in adrenal capsular Ang II contents in SHRSP may be partly due to an enhanced local production of Ang II.
Hypertension 1992 Sep
PMID:Adrenal and circulating renin-angiotensin system in stroke-prone hypertensive rats. 151 46

This study examines the changes in the mRNA expression of epidermal growth factor (EGF), EGF receptor (EGFR), platelet derived growth factor (PDGF-B), and transforming growth factor beta (TGF-beta 1) before and after sustained pressor infusion of angiotensin II (Ang II) for 4 weeks. A threefold increase occurred in the levels of EGFR mRNA (17,240 +/- 827 vs 6403 +/- 1372 units, P less than 0.01) and TGF-beta 1 mRNA (1644 +/- 584 vs 475 +/- 30 units, P less than 0.01) only in the aorta and not in the heart and kidney tissues. This increase in both of the above mRNA transcripts highly correlated (r = 0.96 and 0.92, P less than 0.01) with the elevation of blood pressure. The specific binding of 125I-labeled EGF to aortic membranes also increased (11,429 +/- 728 vs 8630 +/- 420 cpm/mg protein, P less than 0.05) with a parallel increase in the protein tyrosine kinase activity of the membranes indicating that the enhanced EGFR mRNA expression resulted in increased activity of a functional receptor. No significant changes were observed in either EGF mRNA or PDGF-B mRNA levels. These findings suggest that EGFR and TGF-beta 1 participate in the long-term progressive pressor response to Ang II and thus potentially in the progression and the maintenance of chronic hypertension.
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PMID:Increased EGF binding and EGFR mRNA expression in rat aorta with chronic administration of pressor angiotensin II. 152 73

The hormonal regulation of sodium and volume homeostasis was investigated in three patients (two related) with the syndrome of familial hyperkalemic acidosis and hypertension with normal glomerular filtration rate. Recumbent plasma renin activity was low during normal sodium intake (135 mmol daily), and the response to upright posture or to low sodium diet (10 mmol daily) was blunted. Recumbent plasma aldosterone levels were normal in two patients and high in one, and the standing values were elevated in one; responses to upright posture were brisk on low sodium diet. Angiotensin II infusion induced a marked increase in plasma aldosterone. Plasma atrial natriuretic peptide was at the upper limit of normal during normal sodium intake, decreased during diuretic therapy, and increased during sodium chloride infusion in one patient. Basal urinary prostaglandin E2, prostaglandin F2 alpha, and 6-ketoprostaglandin F1 alpha excretion rates were decreased, and thromboxane B2 was increased. Total blood and plasma volumes were subnormal, whereas extracellular fluid volume and exchangeable sodium values were close to or above (in one patient) the mean normal values. Chronic treatment with hydrochlorothiazide in two patients corrected the hyperkalemic acidosis and hypertension, but on its discontinuation (in one patient) all biochemical abnormalities promptly reappeared.
Hypertension 1992 Apr
PMID:Endocrine sodium and volume regulation in familial hyperkalemia with hypertension. 153 66


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