Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors studied the incidence of individual aetiological factors which may cause intrauterine interruption of foetal development. The research concerned 26 pregnant women hospitalized in the Ward for Pregnancy Pathology of the Department of Gynaecology and Obstetrics over the period from 1986-1989. The majority of women with this manifested EPH gestosis: essential hypertension was observed in 3 patients (12%). Particular attention was paid to the final stage of delivery and to the Apgar Score. Discussion includes the results of other authors. In the conclusion the importance and significance of this problem are stressed--within the scope of perinatal medicine--in view of the high morbidity and mortality rates among infants.
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PMID:[Etiologic factors in fetal intrauterine growth retardation]. 134 Jun 43

Retrospective evaluation was applied to 162 pregnancies of women with hypertension at the Third Municipal Hospital of Sofia, Department of Obstetrics and Gynaecology, for a period between 1976 and 1980. The birth record in that period amounted to 9348. Hypertension was recorded from 1.7 per cent of the deliveries. All women examined were primiparae. They were subdivided by four groups: essential hypertension, organic hypertension, EPH gestosis, and plug gestosis. Sixty-two patients with an earlier record of EPH gestosis were additionally examined in a follow-up programme, between 1977 and 1980. Most of the hypertension cases were identified as having been different from EPH gestosis. An attempt is made to group hypertension during pregnancy. The authors suggest that higher accuracy of diagnosis will help to reduce the incidence of both essential hypertension and EPH gestosis. An analysis was made of diagnostic and therapeutic approaches, control of labour, and condition of the newborns.
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PMID:[Hypertension, pregnancy and childbirth]. 716 56

This study represents a retrospective analysis of pregnancies with chronic arterial hypertension and their outcomes. The aim was to evaluate the influence of arterial hypertension on 101 essential and 109 cases of secondary hypertension in comparison to the control group consisting of 499 normotensive pregnancies. According to the obtained data, 27.7% of the women with chronic hypertension had proteinuria, 61% had bacteriuria and 58.6% had superimposed EPH gestosis. The occurrence of EPH gestosis among the controls was 5.6%, that is significantly less than in the experimental group (X2 = 282.8%; p < 0.001). The outcomes of pregnancies associated with chronic hypertension were: 19% preterm deliveries compared to the controls in which only 9.2% preterm deliveries occurred (X2 = 14.4; p < 0.001). Newborns from pregnancies with essential hypertension were significantly heavier, weighing 3177 +/- 734 g, than those from pregnancies with secondary hypertension, which weighted 2578 +/- 932 g. Perinatal mortality was higher in the study group and significantly higher in the pregnancies with associated secondary hypertension (30.3%) than in pregnancies associated with essential hypertension (15.8%).
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PMID:[Fetal growth in pregnant women with chronic hypertension]. 817 92

This study evaluated whether hypertensive siblings had excess sharing of RsaI and SstI alleles of the insulin receptor gene compared with a random population. Thirty families consisting of 60 affected individuals with established hypertension were genotyped for the RsaI and SstI restriction fragment length polymorphisms and the resulting genotype data was analysed using the affected pedigree member method of linkage analysis. The hypertensive siblings were found to have increased sharing of INSR alleles; however, this linkage could not be confirmed using a maximum LOD score method. Thus, the results from this study do not support a role for the INSR gene in the genesis of essential hypertension in the population studied.
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PMID:Absence of genetic linkage between polymorphisms of the insulin receptor gene and essential hypertension. 852 86

The association of the polymorphisms of two candidate genes with essential hypertension was studied in 74 hypertensive and 118 normotensive subjects. Two restrictions endonucleases were used: PstI for the insulin receptor gene and PvuII for the apolipoprotein B gene. PstI RFLP in the INSR gene locus consists of two polymorphic alleles P1 (1800bp) and P2 (1500bp). Frequencies of these alleles in general population are 0.15 and 0.85 respectively. The results showed statistically significant association between P1 allele and homozygotus genotype P1P1 for the INSR gene and essential hypertension. Clinical data of homozygotus P1P1 individuals revealed earlier clinical onset and more severe course of the disease. PvuII RFLP in the apoB gene locus consists of two polymorphic alleles Pul (7900bp) and Pu2(5500 bp). Frequencies of these alleles in general population are 0.93 and 0.07 respectively. In the apoB gene analysis Pu1 and Pu2 allele frequencies were similar in both studied groups. However the higher frequency of homozygotus genotype Pu1Pu2 was observed in hypertension.
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PMID:[Polymorphic variability of apolipoprotein B genes and insulin receptor in essential hypertension]. 875 50

Vasopeptidase inhibition is a new concept in cardiovascular therapy. It involves simultaneous inhibition with a single molecule of two key enzymes involved in the regulation of cardiovascular function, neutral endopeptidase (EC 24.11; NEP) and angiotensin-converting enzyme (ACE). Simultaneous inhibition of NEP and ACE increases natriuretic and vasodilatory peptides (including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP] of myocardial cell origin, and C-type natriuretic peptide [CNP] of endothelial cell origin) and increases the half-life of other vasodilator peptides including bradykinin and adrenomedullin. By simultaneously inhibiting the renin-angiotensin-aldosterone system and potentiating the natriuretic peptide system, vasopeptidase inhibitors (VPIs) reduce vasoconstriction and enhance vasodilation, thereby decreasing vascular tone and lowering blood pressure. Omapatrilat, a heterocyclic dipeptide mimetic, is a novel vasopeptidase inhibitor and a single molecule that simultaneously inhibits NEP and ACE with similar inhibition constants. Unlike ACE inhibitors, omapatrilat demonstrates antihypertensive efficacy in low-, normal-, and high-renin animal models. Unlike NEP inhibitors, omapatrilat provides a potent and sustained antihypertensive effect in spontaneously hypertensive rats (SHR), a model of human essential hypertension. In animal models of heart failure, omapatrilat is more effective than ACE inhibition in improving cardiac performance and ventricular remodeling and prolonging survival. Omapatrilat effectively reduces blood pressure, provides target-organ protection, and reduces morbidity and mortality from cardiovascular events in animal models. Omapatrilat is the first VPI to enter advanced USA clinical trials. Omapatrilat appears to be a safe, well-tolerated and effective antihypertensive in humans. Vasopeptidase inhibition is a novel and efficacious strategy for treating cardiovascular disorders, including hypertension and heart failure, that may offer advantages over currently available therapies.
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PMID:Vasopeptidase inhibition: a new concept in blood pressure management. 1034 Aug 42

Although conduit arteries develop hypertrophy after chronic NO synthesis blockade, resistance arteries remodel without hypertrophy under the same conditions. Similar findings have been described in essential hypertension. We postulated that this regional difference may be related to a heterogeneous effect of endogenous NO on proliferation along the vascular tree. Newly synthesized proteins were radiolabeled in vivo with [(3)H]L-leucine in basal conditions and during NO synthase inhibition, with or without PD98059 (inhibitor of the extracellular signal-regulated kinases [ERK] 1/2). Blocking the generation of NO by 3 different L-arginine analogues increased protein synthesis by an average of 75% in the aorta, in association with enhanced ERK 1/2 phosphorylation. PD98059 significantly reduced L-arginine analogue-induced protein synthesis and ERK 1/2 phosphorylation, confirming the involvement of ERK 1/2 as an important signaling element. In small arteries, L-arginine analogues did not influence the extent of protein synthesis, although phosphorylation of ERK 1/2 was also enhanced. To determine the role of NO in a condition of enhanced protein synthesis, angiotensin II was infused for 24 hours. Angiotensin II augmented protein synthesis in mesenteric arteries and the aorta, and was additive to NO synthase blockade in the aorta. In conclusion, endogenous NO exerts a tonic inhibitory influence on aortic growth, with limited impact on small arteries in basal and hypertrophic conditions. This heterogeneous role of NO on vascular growth may explain the heterogeneity of vascular remodeling observed in essential hypertension, a condition associated with endothelial dysfunction.
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PMID:Vessel-specific stimulation of protein synthesis by nitric oxide synthase inhibition: role of extracellular signal-regulated kinases 1/2. 1179 72

An impaired exercise capacity is common in hypertensive patients (pts) and factors affecting exercise capacity are not completely elucidated. The aim of the study was to investigate factors influencing exercise capacity in hypertensive pts Studied group consisted of 41 pts (18 males, 23 females) mean age 54.2 +/- 11.9 with essential hypertension and without coronary artery disease. Each patient underwent an echocardiographic examination followed by treadmill exercise test. Echocardiographic assessment comprised estimation of left ventricular (LV) mass index (LVMI), pattern of LV geometry, ejection fraction (LVEF), fractional shortening (LVFS), peak and integral velocities of early (E, Ei) and late (A, Ai) transmitral flow, deceleration time of E wave (DT), isovolumic relaxation time (IVRT), duration of A wave (A-dur), total ejection isovolume index (TEI), E (ETT) and A (ATT) wave transit time to the LV outflow tract, flow propagation velocity of E wave (EP), peak and integral velocities of systolic (S, Si), diastolic (D, Di) and atrial reversal (AR, ARi) pulmonary venous flow, duration of AR wave (AR-dur), acceleration (SAT) and deceleration (SDT) of systolic pulmonary venous flow, systolic forward fraction of pulmonary venous flow (SFF). Exercise capacity was assessed by exercise time and total workload expressed in MET. Significant correlations were found for MET and: age (r = -0.49, p < 0.001), A (r = -0.62, p < 0.001), E/A ratio (r = 0.55, p < 0.004), Di (r = 0.55), p < 0.004), ARi (r = -0.38, p < 0.01), SFF (r = 0.46, p < 0.002). Exercise time correlated with A (r = -0.61, p < 0.001), E/A ratio (r = 0.41, p < 0.04), Di (r = 0.51, p < 0.009), ARi (r = -0.35, p < 0.02), SFF (r = -0.51, p < 0.008), S/D ratio (r = -0.47, p < 0.01). Other investigated parameters did not correlate with both MET and exercise time. By stepwise multiple linear regression analysis Di and ARi were the only determinants of MET (multiple r = 0.85, p < 0.0001) whereas A and Di turn out to be the only independent predictors of exercise time (multiple r = 0.76, p < 0.0004). In hypertensive pts: 1. diastolic function of LV is a principle determinant of exercise capacity, 2. integral velocity of diastolic and atrial reversal pulmonary venous flow and peak velocity of late transmitral flow are the best predictors of exercise tolerance.
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PMID:[Determinants of exercise capacity in hypertensive patients]. 1292 68

The genetic and environmental heterogeneity of essential hypertension is responsible for the individual variability of antihypertensive therapy. An understanding of the molecular mechanisms underlying hypertension and related organ complications is a key aspect for developing new, effective, and safe antihypertensive agents able to cure the cause of the disease. Two mechanisms, among others, are involved in determining the abnormalities of tubular Na+ reabsorption observed in essential hypertension: the polymorphism of the cytoskeletal protein alpha-adducin and the increased circulating levels of endogenous ouabain (EO). Both lead to increased activity and expression of the renal Na+-K+ pump, the driving force for tubular Na transport. Morphological and functional vascular alterations have also been associated with EO. Rostafuroxin (PST 2238) is a new oral antihypertensive agent able to selectively antagonize EO, adducin pressor, and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, Rostafuroxin antagonizes EO triggering of the Src-epidermal growth factor receptor (EGFr)-dependent signaling pathway leading to renal Na+-K+ pump, and ERK tyrosine phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by nanomolar ouabain. A very high safety ratio and an absence of interaction with other mechanisms involved in blood pressure regulation, together with initial evidence of high tolerability and efficacy in hypertensive patients, indicate Rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and EO-hypertensive mechanisms.
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PMID:Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension. 1646

Essential hypertension is a heterogeneous multifactorial syndrome associated with a high cardiovascular risk. A multiple choice of antihypertensive drugs is available; however, a high individual variability to the antihypertensive therapy is still responsible for a modest reduction of the CV risk and not satisfactory control of blood pressure levels. The success of future hypertension treatment will depend upon the understanding of the genetic molecular mechanisms operating in subsets of patients, and the ability of new drugs to specifically correct such alterations. Two mechanisms, among others, are involved in determining the abnormalities of tubular Na(+) reabsorption observed in essential hypertension: the polymorphism of the cytoskeletal protein alpha-adducin and the increased circulating levels of endogenous ouabain (EO). Both lead to increased activity and expression of the renal Na-K pump, the driving force for tubular Na transport. Morphological and functional cardiovascular alterations have also been associated with adducin and EO. Rostafuroxin is a new oral antihypertensive agent able to selectively antagonize adducin and EO hypertensive and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, Rostafuroxin normalizes the enhanced activity of the Na-K pump induced by adducin mutation and antagonizes the EO triggering of the Src-EGFr-dependent signaling pathway leading to renal Na-K pump, and ERK Tyrosin phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by ouabain. A very high safety ratio and an absence of interaction with other mechanisms involved in blood pressure regulation, together with initial evidence of high tolerability and efficacy in hypertensive patients, indicate Rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and EO-hypertensive mechanisms. Currently, a phase II multicenter European clinical trial is ongoing for providing the proof of concept that such a compound is effective in the subset of patients where these two mechanisms are at work.
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PMID:Targeting Ouabain- and Adducin-dependent mechanisms of hypertension and cardiovascular remodeling as a novel pharmacological approach. 1709 40


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