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

We investigated the relation between atrial natriuretic factor (ANF) gene expression and the status of the renin-angiotensin system (RAS) in aortic tissue in rats made hypertensive by either aortic banding or by deoxycorticosterone acetate (DOCA)-salt administration. These experimental models of hypertension are known to have differences in terms of the status of RAS. ANF messenger RNA (mRNA) levels were measured in aortic tissue by using a newly developed quantitative competitive reverse transcription polymerase chain reaction (QC-RT-PCR) technique. Changes in the proportions of alpha1 and alpha2 isoforms of Na+K+-adenosine triphosphatase (ATPase) mRNA levels were used as indicators of aortic hypertrophy. Treatment with DOCA alone, salt alone, or DOCA-salt for 5 weeks increased aortic-weight/body-weight ratio and aortic angiotensinogen mRNA levels, but did not change alpha1 or alpha2 Na+K+-ATPase mRNA levels. Aortic ANF mRNA levels had a tendency to increase after treatment with DOCA, salt, or DOCA-salt, but this change did not reach statistical significance. Suprarenal aortic banding for 6 weeks or 12 weeks increased aortic-weight/body-weight ratio (12 weeks), decreased alpha2 Na+K+-ATPase and angiotensinogen mRNA levels, but did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Treatment with ramipril, an angiotensin-converting enzyme (ACE) inhibitor was carried out for 6 weeks just after aortic banding (prevention experiment) or after 6 weeks in rats that were banded for the previous 6 weeks (regression experiment). High-dose ramipril (1 mg/kg)--a treatment known to inhibit both tissue and circulating RAS--normalized aortic-weight/body-weight ratio, and also normalized alpha2 Na+K+-ATPase mRNA levels. Aortic angiotensinogen mRNA levels of banded rats treated with high-dose ramipril was higher than those of the normal control, sham operated, and banded rats. Treatment with high-dose ramipril did not affect alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. Low-dose ramipril (10 microg/kg)--a treatment that selectively inhibits tissue RAS--normalized aortic-weight/body-weight ratio but did not normalize alpha2 Na+K+-ATPase mRNA levels (regression experiment) or angiotensinogen mRNA levels (prevention experiment) and did not change either alpha1 Na+K+-ATPase mRNA levels or ANF mRNA levels. The results suggest that, in contrast to previous findings in heart and kidney, the regulation of ANF mRNA levels in aortic tissue is largely independent of pressure load, volume load, and plasma or tissue RAS. It is suggested that any antihypertrophic actions of ANF may be mediated by the increased circulating ANF levels and its interaction with its receptor or through CNP.
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PMID:Regulation of aortic atrial natriuretic factor and angiotensinogen in experimental hypertension. 986 8

Ouabain has been shown to be an endogenous hormone that is synthesized and released from the adrenal cortex and is present in nanomolar to subnanomolar concentrations in plasma. It has been proposed that endogenous ouabain can increase vascular resistance and induce hypertension. This substance inhibits the Na(+)-pump activity, which leads to intracellular Na+ accumulation and ultimately to increased vascular tone. It is also suggested that circulating ouabain influences the vascular smooth muscle response to vasopressor substances. However, the mechanisms by which low concentrations of ouabain influence the smooth muscle, directly or acting through the endothelium, have not been completely elucidated. We tested the hypothesis that the endothelium exerts a modulatory effect on the actions of ouabain. In these studies, isolated rat-tail vascular bed preparations obtained from normotensive animals were used. The effects of 10 nM ouabain on the reactivity of the vascular smooth muscle to phenylephrine were determined under conditions in which endothelial function was preserved or reduced by endothelial removal and treatment with N(omega)-nitroL-arginine methyl ester (L-NAME) or potassium channel blocker (tetraethylammonium; TEA). Results showed that ouabain enhanced the reactivity to phenylephrine. The enhancement of the reactivity to phenylephrine produced by ouabain was potentiated by deendothelialization and by using TEA, but it was reduced by treatment with L-NAME. The effect of 10 nM ouabain on the functional activity of the Na+,K(+)-adenosine triphosphatase (ATPase) also was evaluated. Na+,K(+)-ATPase activity was reduced after 1-h treatment with ouabain. These results suggested that low concentrations of ouabain reduced the functional activity of the Na+,K(+)-ATPase and stimulated the release of a potassium channel opener, suggesting that the effects of ouabain are partially modulated by the endothelium.
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PMID:The influence of nanomolar ouabain on vascular pressor responses is modulated by the endothelium. 1059 34

Vascular remodeling is a key feature of many pathologic states, including atherosclerosis, or hypertension. Vascular smooth muscle cells participate in determining the vessel structure by several mechanisms such as cell migration, cell growth, or cell death (necrosis or apoptosis). Here we report that thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ -adenosine triphosphatase (ATPase), is able to induce apoptosis in human vascular smooth muscle cells (HVSMCs). Apoptosis was assessed by three different methods: differential chromatin binding dye staining. cytoplasmic histone-associated DNA fragments detection by enzyme-linked immunosorbent assay (ELISA) and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). When HVSMCs were treated for 1 h with thapsigargin (100 nM-10 microM), there was a concentration-dependent increase in both parameters 24 h after the thapsigargin pulse. When a time-course experiment was performed, both parameters were significantly enhanced from 3 to 6 h after the exposure to thapsigargin. We conclude that thapsigargin promotes apoptosis in HVSMCs, providing a useful tool for the study of programmed cell death in human vascular smooth muscle.
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PMID:Thapsigargin induces apoptosis in cultured human aortic smooth muscle cells. 1106 29

The association between excess glucocorticoids and hypertension has been much discussed but poorly understood. From both clinical observations and laboratory studies, it is clear that glucocorticoids exert their effects at many different sites responsible for blood pressure regulation. Isoforms of the enzyme 11ss-hydroxysteroid dehydrogenase (11ss-HSD), located in steroid-responsive tissues, metabolize endogenously produced glucocorticoids. These enzymes limit steroid access to mineralocorticoid and/or glucocorticoid receptors. In the kidney, synthetic and endogenous glucocorticoids are capable of enhancing transepithelial sodium transport in the presence of 11ss-HSD inhibition. Proximal tubule reabsorption of sodium can be indirectly augmented after chronic exposure to glucocorticoids. In this segment, steroids have a permissive effect, increasing the expression of both Na(+), K(+) adenosine triphosphatase along the basolateral membrane and Na(+)-H(+) exchanger along the apical membrane of epithelial cells. Although glucocorticoids themselves produce no increase in sodium reabsorption in this segment, angiotensin II-stimulated sodium transport is significantly greater in proximal tubular cells pretreated with glucocorticoids. The increased transport in distal renal segments is more direct and stems in part from glucocorticoid cross-over binding to mineralocorticoid receptors. In vascular tissue, synthetic and endogenous glucocorticoids, after inhibition of the dehydrogenase reaction, magnify the response to circulating vasoconstrictors. The effects of glucocorticoids in vascular tissue is indirect, upregulating the expression of receptors to many vasoconstrictors and downregulating the effects of potential vasodilators. Thus, glucocorticoids have the potential to alter both circulating volume and vascular resistance.
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PMID:Insights Into Glucocorticoid-Associated Hypertension. 1113 61

Lead is associated with elevated blood pressure, although the mechanism of action is unknown. Genetic differences in sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase) could explain some of the variation in the strength of the blood pressure-blood lead relation that has been observed in previous studies. In 1996-1997, the authors studied the association of blood pressure, hypertension prevalence, and polymorphisms in the gene for the alpha 2 subunit of Na(+)-K(+)ATPase (ATP1A2) among 220 former organolead manufacturing workers from New Jersey. Subjects were genotyped for a restriction fragment length polymorphism (RFLP) on the ATP1A2 gene. The association between blood lead and blood pressure was stronger among persons who were homozygous for the variant allele. Genotype was also associated with hypertension (adjusted odds ratio = 7.7; 95% confidence interval: 1.9, 31.4). Finally, the variant allele was 1.8 times more common among African Americans than among Caucasians. The RFLP may indicate susceptibility to the effect of lead on blood pressure. Moreover, the alpha 2 gene (or a closely linked gene) may contribute to the pathophysiology of hypertension. However, because the number of subjects (especially African Americans) with the susceptible genotype in this study was small, these observations should be considered preliminary.
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PMID:Relation of alleles of the sodium-potassium adenosine triphosphatase alpha 2 gene with blood pressure and lead exposure. 1125 61

The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride (NaCl) per kilogram (kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) pump activity was measured by potassium (K+)-induced relaxation (with or without ouabain) following precontraction with 10(-7) M noradrenaline. The KATP channel was studied by measuring the relaxation response to cromakalim, precontracted with either 10(-7) M noradrenaline or 60 mM potassium chloride (KCl). The Na-K ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K(+)-induced contraction. Cromakalim produced relaxation of noradrenaline-precontracted rings from the control rats; rings from salt-loaded rats showed significantly less relaxation than control (p < 0.05) under similar conditions. During K(+)-induced precontraction, cromakalim produced a weak biphasic response in the control rings--an initial relaxation and then a reversal. Cromakalim produced further contraction of K(+)-induced precontraction in the salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.
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PMID:Salt-induced hypertension in rats alters the response of isolated aortic rings to cromakalim. 1139 81

Potential mechanisms underlying prenatal programming of hypertension in adult life were investigated using a rat model in which maternal protein intake was restricted to 9% vs. 18% casein (control) during pregnancy. Maternal low protein (MLP) offspring exhibit glucocorticoid-dependent raised systolic blood pressure throughout life (20-30 mm Hg above the control). To determine the molecular mechanisms underlying the role of alterations in glucocorticoid hormone action in the prenatal programming of hypertension in MLP offspring, tissues were analyzed for expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11betaHSD1, 11betaHSD2, and corticosteroid-responsive Na/K-adenosine triphosphatase alpha1 and beta1. GR protein (95 kDa) and messenger RNA (mRNA) expression in kidney, liver, lung, and brain was more than 2-fold greater in MLP vs. control offspring during fetal and neonatal life and was more than 3-fold higher during subsequent juvenile and adult life (P < 0.01). This was associated with increased levels of Na/K-adenosine triphosphatase alpha1- and beta1-subunit mRNA expression. Levels of MR gene expression remained unchanged. Exposure to the MLP diet also resulted in markedly reduced levels of 11betaHSD2 expression in the MLP placenta on days 14 and 20 of gestation (P < 0.001), underpinning similar effects on 11betaHSD2 enzyme activity that we reported previously. Levels were also markedly reduced in the kidney and adrenal of MLP offspring during fetal and postnatal life (P < 0.001). This programmed decline in 11betaHSD2 probably contributes to marked increases in glucocorticoid hormone action in these tissues and potentiates both GR- and MR-mediated induction of raised blood pressure. In contrast, levels of 11betaHSD1 mRNA expression in offspring central and peripheral tissues remained unchanged. In conclusion, we have demonstrated that mild protein restriction during pregnancy programs tissue-specific increases in glucocorticoid hormone action that are mediated by persistently elevated expression of GR and decreased expression of 11betaHSD2 during adult life. As glucocorticoids are potent regulators not only of fetal growth but also of blood pressure, our data suggest important potential molecular mechanisms contributing to the prenatal programming of hypertension by maternal undernutrition in the rat.
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PMID:The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. 1141 3

Patients with diabetes mellitus have a high incidence of heart failure, which contributes significantly to their increased cardiovascular morbidity and mortality. One of the major complications of diabetes is the development of cardiomyopathy, a condition characterized by defects of contractile function in the absence of significant coronary artery disease or systemic hypertension. Experimental data in animal models show that contractile depression begins as early as 1 week after induction of diabetes, and the dysfunction is related to an isomyosin distribution shift from V(1) with high adenosine triphosphatase (ATPase) to V(3) with low ATPase activity. Moreover, diabetes is associated with an increased or poorly regulated rate of amino acid catabolism at the cardiac level. Abnormal responses to acute left ventricular (LV) overload induced by exercise (isometric or isotonic) have been demonstrated in patients with diabetes. Impaired augmentation of LV ejection fraction occurs in up to 40% of patients with diabetes. Analysis of the LV afterload-pump function (LV circumferential wall stress-ejection fraction) relationship shows that defective contractile recruitment is the main cause of this anomaly. Exercise-induced LV dysfunction may be the first manifestation of cardiac involvement in patients with diabetes. Increasing the supply of amino acids in addition to conventional therapy significantly attenuates this phenomenon. Although the precise underlying pathophysiologic mechanism is not completely known, these observations may eventually be important in designing an optimal dietary or supplemental approach for patients with diabetes in order to prevent progressive myocardial dysfunction.
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PMID:Early myocardial dysfunction in the diabetic heart: current research and clinical applications. 1509

Women diagnosed as having hysterocarcinoma (HC) demonstrate even prior to surgical intervention manifest abnormalities in metabolic indices, such as increase in the level of medium-size molecules, decrease in the blood content of adenosine triphosphatase, and profound disturbances in microhemodynamics. The most significant abnormalities of metabolism and microcirculation occur in clinical stage III HC against the background of concomitant somatic pathology, diabetes mellitus, arterial hypertension, adiposis in particular.
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PMID:[The endogenous intoxication syndrome and indices of the adenyl system and microhemodynamic in patients with uterine cancer]. 1531 95

The search for an endogenous digitalis has led to the identification of the cardenolides ouabain and digoxin and the bufadienolide marinobufagenin in mammalian tissues and biological fluids. Ouabain's release from adrenal glands is under the control of epinephrine and angiotensin II; hence, its blood concentration changes rapidly on physical exercise. It also is controlled by brain areas sensing cerebrospinal Na+ concentration and apparently the body's K+ content because urinary K+ loss leads to an increase in its plasma concentration as well. Long-term treatment of rats with ouabain results in arterial hypertension, and 50% of Caucasians with low-renin hypertension have increased plasma concentrations of this cardenolide. Levels of digoxin, which is synthesized from acetate in adrenal glands, increase slightly in blood on prolonged exercise. It counteracts the hypertensinogenic action of ouabain in rats, as does the ouabain antagonist PST 2238. The plasma concentration of the bufadienolide marinobufagenin is increased after cardiac infarction. It may show natriuretic properties because it inhibits the alpha1 isoform of Na+/K+-adenosine triphosphatase (ATPase), the main sodium pump isoform of the kidney, much better than other sodium pump isoforms. These effects of endogenous cardiac glycosides are observed at concentrations that do not inhibit the sodium pump. Apparently, Na+/K+-ATPase is used by these steroids as a signal transducer to activate tissue proliferation, heart contractility, arterial hypertension, and natriuresis via various intracellular signaling pathways.
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PMID:Endogenous cardiac glycosides: hormones using the sodium pump as signal transducer. 1613 90


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