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

Using cultured neonatal ventricular myocytes, we investigated whether nitric oxide (NO) directly influences myocyte growth. Treatment of myocytes with phenylephrine stimulated growth, as indicated by increases in atrial natriuretic factor, brain natriuretic peptide (BNP) mRNA and BNP secretion, activator protein 1 activity (activation of early-response genes), and total cellular protein content. NO was stimulated by treatment of myocytes with interleukin-1 beta (IL-1 beta) or was generated by the NO donor nitroglycerin, and its effects on total protein content and BNP secretion were measured. Treatment of cardiocytes with 3.4 nmol/L IL-1 beta for 24 hours stimulated NO (nitrite) production by threefold, which resulted from an increase in the inducible isoform of NO synthase mRNA. Dexamethasone inhibited IL-1 beta induction of nitrite production, whereas the protein kinase C inhibitor staurosporine had no effect. IL-1 beta had no effect on either basal or phenylephrine-stimulated protein content but inhibited phenylephrine-stimulated BNP secretion. Nitroglycerin (10(-7) to 10(-3) mol/L) dose-dependently increased NO production; however, only the highest dose (10(-3) mol/L) reduced basal and phenylephrine-stimulated total protein content and BNP secretion. cGMP, a second messenger of NO, had no effect on either basal or phenylephrine-stimulated BNP secretion or total protein content. In conclusion, our data indicate that BNP mRNA is stimulated by phenylephrine as shown previously for atrial natriuretic factor. Although both BNP and total protein content are increased by phenylephrine, these effects are not inhibited by NO. However, IL-1 beta inhibits phenylephrine-stimulated BNP secretion but not total protein content, suggesting that regulation of BNP secretion can be dissociated from total protein synthesis during myocyte growth.
Hypertension 1995 Mar
PMID:Effects of interleukin-1 beta and nitric oxide on cardiac myocytes. 787 68

In 1979, Ulick and New first coined the term Apparent Mineralocorticoid Excess (AME) for a syndrome of hypertension, hypokalaemia, suppressed renin-angiotensin-aldosterone axis and raised urinary ratio of 11 beta-hydroxy to 11-oxo metabolities of cortisol (suggesting a failure of conversion of cortisol to cortisone). In retrospect, the first case was described in 1974 and since then over 20 children have been reported worldwide but only one adult patient. The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) confers aldosterone specificity on intrinsically nonspecific kidney mineralocorticoid receptors by converting the active glucocorticoid cortisol to its inactive 11-oxo form (cortisone). Patients with AME have a deficiency of this enzyme which allows physiological levels of cortisol to flood mineralocorticoid receptors. Dexamethasone, by suppressing adrenal cortisol production, reverts the biochemistry but not usually the BP to normal. Liquorice inhibits 11beta-OHSD by virtue of its active ingredient glycyrrhetinic acid, resulting in an identical clinical picture. Renal 11beta-OHSD is the protagonist in AME but this enzyme is found in many other tissues including liver, placenta and vasculature, and one-third of essential hypertensives have deficient 11beta-OHSD. The placental isoform is thought to be the main barrier to maternal glucocorticoids reaching the fetus. The lowest rat placental 11beta-OHSD activity is found in the largest placentas corresponding to the smallest fetuses (presumably exposed to the highest glucocorticoid levels). This is the group which in humans are most at risk of developing hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apparent mineralocorticoid excess. 806 85

The incidence of hypertension in conditions of chronic glucocorticoid (GC) excess is very high, though the mechanism whereby GC elevate blood pressure is far from being understood. We have recently found that GC markedly increase influx of Na+ in vascular smooth muscle (VSM) cells. We and other investigators have previously described receptors for GC in arterial tissues, and we have now examined whether the effect of GC on Na+ transport in VSM is mediated through these receptors. Vascular smooth muscle cells were cultured from rabbit aortas. The cells were treated for 48 h with 10(-7) mol/L dexamethasone (DEX), in the presence or absence of RU 486, a competitive inhibitor of DEX binding to its receptor, or progesterone, an allosteric accelerator of DEX dissociation from the receptor. Unidirectional influx of Na+ was measured with 22Na as tracer. Dexamethasone more than doubled the influx rate of Na+, RU 486 completely prevented this increase, and progesterone reduced the DEX-induced increase by approximately 80%. The time of the cell exposure to DEX necessary for the DEX effect to occur was 4 to 6 h, with a maximal effect at 48 h, suggesting a genomic effect. Addition of protein synthesis inhibitors, actinomycin D or cycloheximide, to VSM cells cultured in the presence of DEX prevented the increase of Na+ influx by DEX.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoids regulate Na+ transport in vascular smooth muscle through the glucocorticoid receptor-mediated mechanism. 811 Apr 26

Vasoconstrictive peptides and prostanoids have been implicated in the pathogenesis of hypertension and vasospasm. Recently, we have shown that human cerebromicrovascular endothelium [human brain endothelial cells (HBEC)] constitutively produces both endothelin-1 (ET-1) and prostanoids. The vasoactive peptides, arginine vasopressin (AVP) or angiotensin II (ANG II), stimulated secretion of both immunoreactive ET-1 and prostanoids from HBEC by a receptor-mediated induction of phospholipase C (PLC) and PLA2. The release of constitutive or AVP- or ANG II-induced ET-1 occurred at different rates during the 24-h incubation of HBEC in serum-free medium. The temporal profile of AVP-stimulated production of prostanoids differed from that of ANG II. AVP-induced release of prostaglandin D2 (PGD2) persisted for 24 h, whereas ANG II-stimulated PGD2 was only seen during the first 4 h of incubation. ANG II maximally stimulated PGI2 secretion during the 4- to 8-h interval, whereas AVP did not stimulate PGI2 secretion. Dexamethasone (Dxm), indomethacin (Indo), and nordihydroguaiaretic acid, the respective inhibitors of PLA2-cyclooxygenase II, cyclooxygenase, and lipoxygenase, increased both constitutive and AVP- or ANG II-stimulated secretion of ET-1. Dxm also decreased AVP- or ANG II-stimulated production of PGD2 and PGF2 alpha. These results indicate an interrelationship between HBEC production of ET-1 and prostanoids, which may play a role in regulating cerebral microcirculation.
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PMID:Vasoconstrictive peptides induce endothelin-1 and prostanoids in human cerebromicrovascular endothelium. 816 28

Previous studies have indicated that ouabain-sensitive cation transport is increased in arteries obtained from rats with glucocorticoid-induced hypertension. However, it remained unclear whether this effect reflected direct glucocorticoid activation or rather depended on the elevated arterial pressure per se. In the present study, we examined the effect of dexamethasone on cultured rat aortic smooth muscle cells. Dexamethasone (10(-9) mol/L) increased ouabain-sensitive 86Rb uptake by about 50% (control: 16.5 +/- 1.6 pmol/mg protein/10 min; dexamethasone 10(-9) mol/L: 24.4 +/- 1.3 pmol/mg protein/10 min). The effect was not apparent until 18 h of incubation and was partly inhibited by the mineralocorticoid antagonist spironolactone. Dexamethasone also increased membrane potential in these cells by an average of 9.5 mV (control: -43.3 +/- 4 mV; dexamethasone: -52.8 +/- 4 mV), presumably reflecting increased intracellular K+ activity as a result of dexamethasone's effect on the Na,K pump. These results suggest a direct effect of glucocorticoids on arterial Na,K pump. The physiopathological significance of this effect remains to be determined.
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PMID:Dexamethasone enhances active cation transport in cultured aortic smooth muscle cells. 817 49

Local or tissue renin angiotensin systems are thought to participate in cardiovascular regulation. However, little information is available on the mechanisms by which renin and angiotensinogen synthesis and secretion are regulated in these tissues. In view of the importance of steroid hormones in the regulation of hepatic angiotensinogen, we have examined the effects of dexamethasone, ethinyl estradiol, or dihydrotestosterone on angiotensinogen gene expression in peripheral or cerebral tissues of Wistar Kyoto (WKY) or spontaneously hypertensive rats (SHR). Following a single injection of dexamethasone (7 mg/kg) the concentrations of angiotensinogen mRNA increased in nearly all organs examined. The differences to controls were higher in SHR than in WKY. Dexamethasone in low doses (10 micrograms/kg/day) given for 10 days did not alter angiotensinogen mRNA or blood pressure in control animals, but increased both parameters in the hypertensive strain. The response to a single dose of ethinyl estradiol (3 mg/kg) was not as uniform as that to dexamethasone, and a tendency for a higher sensitivity was found in SHR. High stimulation rates were found in liver and kidneys of both strains. A single dose of dihydrotestosterone (10 mg/kg) did not significantly affect angiotensinogen mRNA in any organ. Only when a high dose of 50 mg/kg was given daily for 20 days, was angiotensinogen mRNA increased in some tissues. These data indicate that glucocorticoids and estrogens participate in the regulation of angiotensinogen gene expression in several extrahepatic tissues. The higher sensitivity to glucocorticoids in SHR may be relevant for the development of hypertension in this strain.
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PMID:Modulation of tissue angiotensinogen gene expression by glucocorticoids, estrogens, and androgens in SHR and WKY rats. 837 10

Accumulating evidence tends to demonstrate that inflammatory processes are responsible for neurological damage and sequelae in bacterial meningitis in children and infants. Massive liberation of bacterial cell wall components (Lipopolysaccharide, acid teichoic polymers) induce a cascade of reactions including the secretion of many cytokines (such as TNF alpha and IL-1 beta) and prostaglandins (such as PAF and PGE2) which in turn leads to the development of cerebral oedema, intracranial hypertension and cerebral blood flow reduction. Dexamethasone (DXM) is effective at the beginning of the inflammatory cascade and its utilisation in the meningitis experimental model in animals has shown significant reduction in the inflammatory response to bacterial meningitis. The first clinical studies using DXM as an adjunctive therapy to antibiotics have demonstrated its beneficial effect in terms of complications and long-term neurological sequelae in Haemophilus influenzae meningitis in children and infants. It seems that a similar effect can be obtained in meningococcal and pneumococcal meningitis. Little information is actually available concerning the use of DXM in penicillin-resistant pneumococcal meningitis. The rare reported cases of ceftriaxone failure with DXM as treatment of penicillin-resistant pneumococcal meningitis had a favorable outcome with the use of vancomycin.
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PMID:[Role of dexamethasone in the treatment of purulent meningitis in infants and in children]. 839 88

We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high-dose dexamethasone (DXM, 40 mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 x 10(9)l (range 6-26 x 10(9)/l) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM. Five patients had a response (i.e. platelet count at least doubled and increased by > 20 x 10(9)/l), including one almost complete remission and four minor responses (MR). Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side-effects (systemic hypertension with stroke and insulin-dependent diabetes, respectively). In our experience, high-dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side-effects in some cases.
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PMID:Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases. 854 98

The objective of this study was to examine the role of dexamethasone on the expression of angiotensin II (Ang II) receptors in cultured rat mesangial cells. Dexamethasone caused concentration- and time-dependent decreases in 125I-[Sar1,Ala8]Ang II binding that were prevented by glucocorticoid receptor inhibition with mifepristone. A lag time of 24 hours and a dexamethasone concentration of at least 10 nmol/L were necessary for this effect to occur. Dexamethasone-induced reduction of 125I-[Sar1,Ala8]Ang II binding resulted from decreased Ang II type 1 (AT1) receptor density. No change in the apparent dissociation constant was observed. Dexamethasone also markedly inhibited Ang II-dependent inositol phosphate accumulation. Both reverse transcription-polymerase chain reaction and Northern blot analysis using specific short probes from the 3' noncoding region of the cDNA demonstrated the presence of AT1A and AT1B receptor mRNAs in rat mesangial cells, with a slight predominance of AT1B. Therefore, we studied the effect of dexamethasone on the expression of these two subtypes in rat mesangial cells. Dexamethasone produced a time-dependent decrease of AT1B receptor mRNA that was apparent after 6 hours of incubation, whereas AT1A receptor mRNA did not change. Mifepristone also suppressed the dexamethasone-induced decrease in AT1B receptor mRNA. In conclusion, glucocorticoids diminish Ang II receptor density at the mesangial cell surface through a mechanism that implies successive interaction with the glucocorticoid receptor and specific reduction in AT1B receptor mRNA expression. This differential regulation of both AT1 receptor subtypes might allow glucocorticoids to exert adjusted effects in their various target tissues.
Hypertension 1996 Apr
PMID:Regulation of angiotensin II receptor subtypes by dexamethasone in rat mesangial cells. 861 62

1. The role of genetically determined changes in adrenal steroid production, metabolism and action in the pathogenesis of cardiovascular disease in man is considered by studying three loci that are important in corticosteroid function. 2. Variation at the glucocorticoid receptor locus can be identified as a biallelic restriction fragment length polymorphism (Bcl1); subjects with contrasting genotypes show altered skin vasoconstrictor responses to topically applied budesonide without any significant change in leucocyte receptor binding characteristics. 3. In a case control study of patients with essential hypertension, we have shown evidence of reduced 11 beta-hydroxysteroid dehydrogenase activity, with an elevated ratio of cortisol to cortisone metabolites in urine. 4. The genes encoding 11 beta-hydroxylase and aldosterone synthase are highly homologous. Studies in the Milan hypertensive rat show variation at this locus, which may account for the increased steroid synthesis noted in the hypertensive strain; in man, a chimaeric gene comprising 5' regulatory regions from 11 beta-hydroxylase and 3' coding sequence from aldosterone synthase accounts for the autosomal dominant condition Dexamethasone Suppressible Hyperaldosteronism. Variation in the precise location of the crossover site between the two genes does not account for the observed phenotypic heterogeneity in this condition. 5. Measurement of basal plasma steroid levels in subjects with essential hypertension show an increased ratio of 11-deoxycortisol/cortisol, consistent with reduced activity of 11 beta-hydroxylase in the zona fasciculata. 6. In summary, three loci involved in corticosteroid synthesis, metabolism and action can independently affect cardiovascular phenotypes; their roles in determining pathophysiological changes, including hypertension, remain to be studied.
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PMID:Corticosteroids in essential hypertension: multiple candidate loci and phenotypic variation. 871 73


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