UMLS:C0020538 - FACTA Search

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

An 11-year-old girl was referred with hypertension, hypokalemia, low renin activity, metabolic alkalosis and hyperaldosteronism. Adrenal computed tomography revealed the presence of a large left adrenal adenoma of 4 x 4.5 cm in size. Following adrenalectomy, the child presented an unusual acute salt-loosing syndrome which necessitated administration of a large quantity of sodium chloride and corticoids. The cells from the tumor were plated. They rapidly proliferated to a monolayer. After incubation for 24 h, basal production of aldosterone (55.4 +/- 9.07 pmol/ml) was observed. This production was stimulated by the presence of ACTH 10(-8) M and KCl 55 mM; angiotensin II 10(-8) M failed to enhance aldosterone secretion. In the four experimental conditions, however (control, ACTH, angiotensin II and KCl), ANF 10(-8) M decreased aldosterone secretion. We conclude that hyperaldosterone secretion by an adrenal adenoma is not due to resistance to the inhibitory effect of ANF but rather to cell multiplication itself. In this patient, the post-surgical salt-loosing syndrome was attributed to the combined effect of the chronic state of high ANF, low potassium and low ACTH in the contralateral gland on the one hand and a certain degree of transitory renal unresponsiveness of the renal distal tubule to aldosterone on the other.
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PMID:An unusual case of an aldosterone-producing adenoma in a prepubertal girl with severe post-surgical adrenal suppression. 784 16

We have examined the effects of the natriuretic peptides on DNA synthesis in primary cultures of neonatal rat cardiac fibroblasts. Binding analysis using 125I-labeled atrial natriuretic peptide identified a single class of high-affinity binding sites (Kd = 0.03 +/- 0.01 nmol/L) in these cells. Of these sites, 80% appear to be of the natriuretic peptide C receptor subtype, with the remainder being A and B receptor subtypes. Northern blot analysis confirmed the presence of all three natriuretic peptide receptors in these cells. Atrial natriuretic peptide (10(-7) mol/L) effected a modest but consistent reduction in both agonist- and stretch-stimulated [3H]thymidine incorporation (17% to 41%). Moreover, brain natriuretic peptide (10(-7) mol/L), C-type natriuretic peptide (10(-7) mol/L), and des-[Gln18,Ser19,Gly20,Leu21,Gly22]-ANF 4-23-NH2 (10(-7) to 10(-6) mol/L) all proved capable of antagonizing growth factor-dependent [3H]thymidine incorporation (the inhibition ranged from 14% to 28%) and cell proliferation, suggesting that all three natriuretic peptide receptor subtypes are involved in the regulation of mitogenesis in these cultures. The inhibition by atrial natriuretic peptide was amplified by cotreatment with phosphodiesterase inhibitors. Similar reduction in [3H]thymidine incorporation was seen after treatment with 8-bromo-cGMP (10(-4) to 10(-3) mol/L) or nitroprusside (10(-4) to 10(-3) mol/L). These results suggest an important paracrine role for the natriuretic peptides in regulating fibroblast growth during cardiac hypertrophy.
Hypertension 1995 Feb
PMID:Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. 784 72

The heart has an endocrine activity which depends on the secretion of a natriuretic, diuretic and hypotensive factor contained in osmophilic, secretory granules localized in the myocardiocytes and called "atrial specific granules" (the atrial natriuretic factor, ANF). In this paper, the relationship between these specific granules and renovascular hypertension elicited by the constriction of both renal arteries was investigated at the electron microscope level during the acute, subacute and chronic phases of hypertension. Male Wistar CHbb THOM rats were divided in three groups: 1) clipped rats; 2) sham operated rats; 3) ether anesthesia as unique manoeuver 48 h before decapitation. Blood pressure increased progressively after the constriction of both renal arteries. The atrial specific granules were not affected by ether anesthesia alone; 48-72 h after clipping the granules almost disappeared and this situation persisted up to the 6th week. In sham operated rats the picture was very similar to the clip rats 48 and 72 h after surgery (severe granule disappearance); in contrast, at one, two and six weeks after surgery, the granularity of cardiomyocytes in sham rats was absolutely restored. It is concluded that: 1) similarities in morphology of atrial specific granules in sham and clip rats 48 and 72 h after surgery would suggest that stress plays a primary role in determining the observed images; 2) thereafter, the contrast between sham and clip rats 1, 2 and 6 weeks after surgery would indicate that the ANF is linked to the subacute and chronic regulation of renovascular hypertension.
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PMID:Ultrastructural study of atrial specific granules in experimental renovascular hypertension elicited by the constriction of both renal arteries. 808 46

Inhibitors of the zinc protease neutral endopeptidase (NEP, EC 3.4.24.11) offer significant therapeutic interest as antihypertensives due to their ability to potentiate the biological action of the circulating natriuretic hormone ANF (atrial natriuretic factor). N-Phosphonomethyl dipeptides bearing a central (4-phenyl)phenylalanine residue have been designed to exert potent and selective NEP inhibition. In particular, (S)-3-[N-[2- [(phosphonomethyl)amino]-3-(4-biphenylyl)propionyl]amino]propionic acid (10a) (CGS 24592) displayed high inhibitory potency in vitro (IC50 = 1.9 +/- 0.1 nM) and a long plasma half-life in rats but lacked oral bioavailability. This drawback was overcome by using esterase-sensitive (acyloxy)alkyl phosphonates. More remarkable, several diaryl phosphonate derivatives of 10a also performed as effective prodrugs. Specifically, the structurally simple diphenyl phosphonate 18 (CGS 25462) induced potent inhibition of NEP ex vivo for at least 8 h after oral administration to rats (30 mg/kg). Its antihypertensive effect was demonstrated in DOCA-salt rats. At 30 mg/kg orally, 18 caused a significant reduction in mean arterial pressure measuring -35 +/- 7 mmHg at 5-h postdosing. The alpha-aminomethyl phosphonate 18 represents a new generation of selective NEP inhibitors that combine high potency, long duration of action, and oral bioavailability. Therefore, it holds promise as a novel therapeutic agent for the treatment of human hypertension and congestive heart failure.
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PMID:N-Phosphonomethyl dipeptides and their phosphonate prodrugs, a new generation of neutral endopeptidase (NEP, EC 3.4.24.11) inhibitors. 812 Aug 68

In the present studies we have shown that atrial natriuretic factor (peptide) receptor of ANF-R2/ANP-C type is coupled to adenylyl cyclase/cAMP signal transduction system through Gi-regulatory protein and is implicated in mediating some of the physiological responses of atrial natriuretic factor or peptide (ANP). ANF-R2/ANP-C receptor-mediated adenylyl cyclase inhibition was altered in hypertension. This alteration was tissue specific. In heart, aorta, brain and adrenal, the extent of inhibition of adenylyl cyclase by ANP was enhanced in SHR as compared to age-matched WKY, whereas in platelets, the ANP-mediated inhibition was completely attenuated. The enhanced inhibition of adenylyl cyclase by ANP was also observed in heart and aorta from DOCA-salt hypertensive rats. In addition, the augmented inhibition of adenylyl cyclase by ANP was observed in 2 weeks and older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats, the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of DOCA-salt treatment when the blood pressure was also enhanced, however one week older SHR but not in 3-5 days old SHR. Similarly, in DOCA-salt hypertensive rats, the enhanced inhibition of adenylyl cyclase by ANP was observed after 2 weeks of DOCA-salt treatment when the blood pressure and augmented ANP-mediated inhibition of adenylyl of DOCA-salt treatment did not result in an augmented blood pressure and augmented ANP-mediated inhibition of adenylyl cyclase, suggesting that blood pressure increase may be responsible for the enhanced responsiveness of ANP to adenylyl cyclase inhibition. However, in genetic model of hypertension, the increased inhibition of adenylyl cyclase by ANP at 2 weeks of age (when the blood pressure is normal) may be implicated in the pathogenesis of hypertension. The augmented inhibition of adenylyl cyclase in cardiovascular tissues from SHR and DOCA-salt hypertensive rats may be due to the upregulation of ANF-R2/ANP-C receptors or due to the amplification of post-receptor signalling mechanisms.
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PMID:Defective ANF-R2/ANP-C receptor-mediated signalling in hypertension. 856 33

In diabetic patients, several factors contribute to volume expansion and have to be counteracted by humoral and neuronal feedback control systems. We investigated N-terminal proatrial natriuretic factor (ANF1-98) and digoxin-like immunoreactive factor (DLIF), which are two counteracting hormones, and their interrelationship, with additional consideration given to autonomic nervous function in diabetic patients. ANF1-98 and DLIF were measured in 64 diabetic patients. Autonomic nervous function was assessed using nine autonomic nervous function tests. The patients were subdivided into two groups, one with four or more (group 1) and one with less than four abnormal results in autonomic function tests (group 2). Compared with group 2, group 1 demonstrated detectable DLIF levels less often (17.2 vs. 45.7, P = 0.0195) and increased levels of ANF1-98 (mean +/- SEM: 850.0 +/- 108.8 vs. 554.8 +/- 45.9 pmol/L, P = 0.0099). However, the groups did not differ in blood pressure, daily sodium, and daily potassium excretion. The number of abnormal autonomic function tests correlated significantly with ANF1-98 (P = 0.0002). In patients with detectable DLIF, DLIF correlated with ANF1-98 (P = 0.0080). These results demonstrate close interactions between the autonomic nervous system and the two natriuretic hormones. In patients with autonomic nervous dysfunction, higher levels of ANF may possibly compensate for the lack of the natriuretic DLIF to counteract hypertension and chronic volume expansion.
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PMID:Atrial natriuretic factor and digoxin-like immunoreactive factor in diabetic patients: their interrelation and the influence of the autonomic nervous system. 921 23

In insulin-dependent diabetes mellitus (IDDM) elevated exchangeable sodium (Na) levels are found even in the absence of hypertension, but it is not known whether this is associated with increased sensitivity of blood pressure to sodium level. To clarify this issue we compared 30 patients with IDDM (19 without and 11 with microalbuminuria, i.e. more than 30 mg albumin/day) and 30 control subjects matched for age, gender and body mass index. The subjects were studied on the 4th day of a low-salt diet (20 mmol/day) under in-patient conditions and were subsequently changed to the same diet with a high-salt supplement, yielding a total daily intake of 220 mmol Na/day. Circadian blood pressure, plasma renin activity (PRA), plasma atrial natriuretic factor (p-ANF), plasma cyclic guanosine 5'-phosphate (p-cGMP) and urinary albumin were measured. The proportion of salt-sensitive subjects, i.e. showing increment of mean arterial pressure > or = 3 mmHg on high-salt diet, was 43% in diabetic patients (50% of diabetic patients with and 37% without microalbuminuria) and 17% in control subjects (p < 0.05). Lying and standing PRA levels on low- or high-salt diet were significantly lower in diabetic patients than in control subjects. Salt-sensitive diabetic patients had significantly higher lying ANF on high-salt (38.7 +/- 4.2 pmol/l vs 20.1 +/- 2.3 pmol/l, p < 0.005) than on low-salt diet. The results suggest that (i) the prevalence of sodium sensitivity is high in IDDM (ii) sodium sensitivity is found even in the absence of nephropathy as indicated by albuminuria.
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PMID:Increased prevalence of salt sensitivity of blood pressure in IDDM with and without microalbuminuria. 878 18

Isolated hypoaldosteronism is found in 75% diabetics where the disease has persisted for 10 or more years. Sporadically it is found in congenital autonomous neuropathy, in acute glomerulonephritis, in gouty kidney, tubulointerstitial nephritis, after transplantation of the kidney, on mytomycin etc. During dynamic testing of the response of plasma renin activity and aldosterone to the administration of furosemide and a vertical position in diabetics a significantly reduced response was recorded as compared with non-diabetic hypertonic subjects. In 18.3% no response was observed (decompensated form of IHH). Diabetic hypertonics behaved like control hypertonics on long-term beta-blocker treatment. In the decompensated form of IHH after administration of drugs interfering with the activity of SNS-RAAS activity (ACEI, spirolactone etc.) a hyperkalaemic crisis may develop which threatens the patient with acidosis, dehydration, myoplegia, muscular spasms, however, in particular with fatal disorders of the cardiac rhythm. A similar effect may be exerted also by blockers of prostaglandin synthetase (non-steroid antirheumatics) and other drugs. The cause of IHH in diabetics is the coincidence of several pathogenic factors: 1. hypersecretion of ANF with hyperosmolar hyperglycaemic hypervolaemia and hyperfiltration already at the onset of DN, 2. early development of autonomous neuropathy of the sympathetic nerve, 3. reduced renin and prostaglandin formation already in the early stages of DN, 4. reduced extrarenal isorenin formation, 5. reduced conversion of prorenin into active renin, 6. reduced reactivity of the zona glomerulosa to AII, hyperkalaemia and ACTH for its functional reconstruction as a result of periodic activation of contraregulative hormones by fluctuations of the blood sugar level in diabetic patients, 7. reduced response of the distal renal tubule to aldosterone because of tubulointerstitial changes. IHH is thus another serious but rarely diagnosed late complication of diabetes which depends only partly on the stage of DN. It must be, however, diagnosed and respected with regard to the selection of drugs for the treatment of arterial hypertension and the syndrome of insulin resistance and the 5H syndrome resp., i.e. the association of hyperinsulinism which compensates insulin resistance with hyperglycaemia (NIDDM), hypertension, hyperlipoproteinaemia and hirsutism in women (so-called Stein-Leventhal syndrome).
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PMID:[Diabetic nephropathy and isolated hyporeninemic hypoaldosteronism]. 892 9

Growth arrest-specific homeobox (Gax) gene was isolated from rat aorta cDNA library and its expression was largely confined to the cardiovascular tissues. Gax gene was rapidly downregulated by platelet-derived growth factor in vascular smooth muscle cells (VSMCs) and overexpressed Gax was reported to reduce the neointimal thickening after balloon injury in vivo. We have demonstrated that angiotensin II (Ang II) stimulates vascular growth. In contrast, we also reported that C-type natriuretic peptide (CNP) is secreted from vascular endothelial cells to act as a novel endothelium-derived relaxing peptide and inhibits vascular growth via cGMP cascade. In the present study, we examined the effects of Ang II and CNP on Gax gene expression in VSMCs. In quiescent rat aortic VSMCs. Gax mRNA (2 3 kb) level became negligible 6 hours after the addition of Ang II (10(-6) mol/L). The inhibitory action of Ang II on Gax mRNA expression (ED50: 10(-11) mol/L) was almost completely blocked by an AT1R antagonist, CV11974. In contrast, CNP 10(-6) mol/L augmented Gax mRNA expression to exhibit 1.8-fold increase of the control 12 hours after the stimulation. This effect of CNP was mimicked by the addition of 8-bromoadenosine 3'-5'-cyclic monophosphate. The addition of C-ANF[4-23], an atrial natriuretic peptide-C receptor-specific agonist and devoid of stimulating cGMP production, exhibited no effect on Gax mRNA expression. Simultaneous administration of Ang II and CNP revealed that CNP (10(-6) mol/L) significantly attenuated the inhibitory action of Ang II (10(-10) mol/L) on Gax mRNA expression. These results suggest that Gax is a common transcription factor involved in the signaling pathway of vascular growth for Ang II and CNP and regulates the cell cycle and/or phenotype of VSMCs for vascular remodeling in hypertension and atherosclerosis.
Hypertension 1997 Jan
PMID:Opposite regulation of Gax homeobox expression by angiotensin II and C-type natriuretic peptide. 903 31

The main task in hypertension research is to explain genetic causes of a raised blood pressure. It is anticipated that advances in this area will promote not only a better understanding of the pathophysiology of hypertension but will make a more aimed approach to early diagnosis, prevention and therapy of essential hypertension possible. The greatest problems in investigations of the heredity of hypertension are; a) in cardiovascular control mechanisms several genes participate; b) factors of the external environment which act on a long-term basis interfere with the relationship of the genotype and phenotype individually, within the family and regionally; c) the blood pressure is a continuous variable and the definition of the phenotype of hypertension is inaccurate; d) inadequate number of family members where hypertension segregates. New methods in molecular biology and statistical genetics made it possible to assess a number of highly polymorphous genetic signs in several candidate genes and the subsequent investigation of their possible role in the pathogenesis of hypertension. The majority of hitherto accomplished studies was concentrated on genes coding different components of the renin-angiotensin system: renin, ACE, angiotensinogen and angiotensin II receptors. So far the most promising, though not consistent, results were obtained for angiotensinogen and the insulin receptor. Work focused on the relationship of the polymorphism of genes for ANF, growth hormone and kallikrein to essential hypertension is negative. The genetic heterogeneity of the human population, physiological differences in the genesis of high blood pressure in different ethnical groups and inaccurate measurements of specific phenotypes can contribute to different results of different studies.
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PMID:[Molecular genetics methods in the study of hereditary essential hypertension]. 951 Dec 64

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