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

This study examines the role of gluco- and mineralcorticoids in the regulation of the renin-angiotensin system and blood pressure in the spontaneously hypertensive rat (SHR). Effects of adrenalectomy and selective treatment with either aldosterone (30 micrograms/kg/day) or dexamethasone (60 micrograms/kg/day) on plasma renin substrate, active renin (PRA), total renin and blood pressure were studied in 10 week old SHR and control WKY rats. Systolic blood pressure was moderately lower in adrenalectomized rats (129 +/- 2 mm Hg vs 137 +/- 4 mm Hg in control WKY and 145 +/- 4 mm Hg vs 160 +/- 3 mm Hg in control SHR) but could be restored to the control range by aldosterone. Dexamethasone repletion induced substantial increments of systolic blood pressure to comparable levels in both species (202 +/- 8 mm Hg in WKY and 192 +/- 6 mm Hg in SHR). Renin substrate was markedly lower in adrenalectomized, saline repleted rats. This could be reversed by dexamethasone in both species and by aldosterone in WKY rats only. Both PRA and total renin were higher (p less than 0.01) in the adrenalectomized, saline repleted state. This increase was not observed in aldosterone repleted rats. However, dexamethasone inhibited the adrenalectomy associated increase of PRA and total renin in SHR but not in WKY rats. Differences in blood pressure between SHR and WKY persist even in adrenalectomized state despite comparable stimulation of the renin system. Conversely, while blood pressure of both species responds similarly to selective corticosteroids therapy, the response of the renin-angiotensin system in SHR and WKY rats is distinct. Therefore factors other than the adrenal gland and the renin system must be involved in the determination of the high blood pressure in SHR.
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PMID:Corticosteroid modulation of the renin system and blood pressure in the spontaneously hypertensive rat. 664 Sep 69

A study of the adrenal function in patients with essential hypertension was performed using gas-liquid chromatography to separate and measure the daily urinary excretion of individual 17-ketosteroids, pregnanediol and pregnanetriol in basal conditions and after a dexamethasone suppression test. The purpose of the study was to detect alterations of adrenal function possibly indicative of some role of the adrenal cortex in the pathogenesis of hypertension. The results showed normal urinary levels of 17-ketosteroids, pregnanediol and pregnanetriol in most patients. Higher values were observed in the remaining cases. Dexamethasone suppression tests confirmed that steroid excess in these patients was of adrenal origin.
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PMID:Adrenal function and essential hypertension. 664 2

The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was used to study the hormonal control of angiotensinogen synthesis and release in the rat. Dexamethasone administration in vivo resulted in increase in the in vitro rate of release of angiotensinogen by liver slices into the incubation media. This increase was inhibited by actinomycin D, an inhibitor of protein synthesis and vincristine which blocks secretion. Similarly, ethinyl estradiol treatment resulted in a 50% increase in angiotensinogen production. Hyperthyroid state was achieved by injecting rats with L-thyroxine daily for seven days. Hepatic production rate of angiotensinogen rose 21/2-fold above control and was accompanied by increases in plasma angiotensinogen concentration and plasma renin activity. In contrast, plasma angiotensinogen concentration and plasma renin activity were reduced in thyroidectomized rats. The rate of angiotensinogen production by liver slices of these rats decreased by five-fold below that of intact animals. These changes were largely corrected when thyroidectomized rats were treated with replacement doses of L-thyroxine. We conclude that hepatic angiotensinogen biosynthesis is under hormonal control. Glucocorticoid, estrogen and thyroid hormones all stimulate angiotensinogen production. These results may in part explain the pathogenesis of hypertension associated with certain disease states.
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PMID:Hormonal control of angiotensinogen production. 704 Aug 93

Report of the observations of 40 patients suffering from neurocysticercosis, submitted to treatment by praziquantel, administered per os. Dexamethasone was associated to praziquantel in 20 patients. Side effects observed had a transient character. Transient exacerbation or reappearance of the cerebrospinal fluid neurocysticercosis syndrome, both related to the periods of treatment, can be considered an indirect rating of praziquantel action on cysticerci. This episode was observed in 31 patients. Dexamethasone proved sufficient to reduce the intensity of these episodes and of the effects. Evaluation of the 20 patients suffering from forms of the disease characterized by intracranial hypertension, and who had a follow-up of more than 3 months (up to 19 months) showed: disappearance of corticoid-dependence (5/5); disappearance of ventricular dilatation (4/6) appearance or increase inthe number of nodular calcifications (3/6); non-occurrence of new outbreaks of intracranial hypertension in 15 of the 20 cases. Repetitive characteristics of the clinical symptomatology, call for a longer-period observation of patients to allow for conclusion as to the effectiveness of the drug in the treatment of neurocysticercosis.
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PMID:Administration of praziquantel in neurocysticercosis. 710 35

Nitric oxide is a potent endogenous vasodilator that regulates arterial tone. A family of nitric oxide synthases uses L-arginine and L-homoarginine stereospecifically as substrates for nitric oxide production in vivo. By preventing expression of inducible but not constitutive nitric oxide synthases, glucocorticoids differentiate which enzyme in this family is the predominant source of nitric oxide generation in a given situation. We proposed that defective production of nitric oxide produces salt-sensitive hypertension in the Dahl/Rapp rat. Plasma concentrations of L-arginine, citrulline, and ornithine of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats on 8% sodium chloride chow for 1 week did not differ. However, intravenous infusion of L-arginine and L-homoarginine, but not D-arginine, increased urinary excretion of nitrate, the degradation product of nitric oxide, and simultaneously lowered blood pressure in hypertensive SS/Jr rats. Oral L-arginine also prevented development of hypertension and increased urinary excretion of cyclic GMP and nitrate in these rats. Dexamethasone, in a dose that prevented hypotension from parenteral injection of lipopolysaccharide, completely prevented the increase in excretion of cyclic GMP and nitrate, and hypertension resulted despite concomitant treatment with L-arginine. These studies supported an important role of dexamethasone-suppressible nitric oxide synthesis in the prevention of salt-sensitive hypertension in the Dahl/Rapp rat.
Hypertension 1993 Dec
PMID:Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. 750 51

The so-called syndrome of 'apparent mineralocorticoid excess' (AME) is a rare cause of endocrine hypertension thought to result from a defect in the peripheral conversion of cortisol to cortisone. Less than 30 cases have been described. From a consanguineous marriage we present a family comprising 2 and probably 3 affected cases of AME. The index case is a 4-year-old boy with mineralocorticoid hypertension, short stature, failure to thrive, hypokalaemic nephropathy and osteopenia. The ratio of the urinary excretion of tetrahydrocortisone/tetrahydrocortisols was reduced at 0.05 (reference range 1.77-2.11), and the plasma half-life of 3H-11 alpha-cortisol elevated at 152 minutes (reference range 30-50) indicative of severe 11 beta-hydroxysteroid dehydrogenase deficiency. Plasma cortisol concentrations were normal and daily secretion rate reduced. Dexamethasone administration induced a natriuresis in keeping with the observation that cortisol itself is the implicated mineralocorticoid. Treatment with amiloride lowered blood pressure, increased potassium levels, and resulted in an increase in growth rate. The boy's twin brother died at the age of 3.5 years following a trivial diarrhoeal illness and was almost certainly affected. AME was also diagnosed in a younger brother (age 17 months), but both parents are normal. Congenital deficiency of 11 beta-hydroxysteroid dehydrogenase should be considered in any child with mineralocorticoid hypertension and failure to thrive. As cortisol is the 'offending' mineralocorticoid in this condition, the term 'apparent' mineralocorticoid excess is perhaps obsolete.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mineralocorticoid hypertension and congenital deficiency of 11 beta-hydroxysteroid dehydrogenase in a family with the syndrome of 'apparent' mineralocorticoid excess. 755 23

Enhancement of vascular responsiveness is considered to be one of the major contributing factors observed in glucocorticoid-induced hypertension. We examined the effects of glucocorticoids on V1a arginine vasopressin receptor mRNA and protein levels in vascular smooth muscle cells. Dexamethasone (1 mumol/L) produced a 1.8-fold increase in V1a receptor density without changing its affinity. Steady-state values of V1a receptor mRNA, analyzed by Northern blotting, increased 2.7-fold after a 12-hour exposure to dexamethasone. This effect of dexamethasone was blocked by the glucocorticoid antagonist RU38486 and did not occur in the presence of the protein synthesis inhibitor cycloheximide. The V1a receptor gene transcription rate, determined by nuclear run-off assays, was unchanged in cells treated with dexamethasone for 12 hours. Dexamethasone increased the half-life of V1a receptor mRNA by 2.2-fold. These findings suggest that dexamethasone upregulates the expression of the V1a receptor by increasing mRNA stability rather than by gene transcription and that de novo protein synthesis is involved in this regulation.
Hypertension 1995 Oct
PMID:Glucocorticoids regulate V1a vasopressin receptor expression by increasing mRNA stability in vascular smooth muscle cells. 755 28

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.
Hypertension 1993 Jul
PMID:Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. 768 32

It is well-known that atherosclerotic change and hypertension are common manifestations in patients with glucocorticoid excess. We previously reported that pituitary adenylate cyclase activating polypeptide (PACAP), prostaglandin E2 (PGE2) and carbacyclin, a stable analog of prostacyclin, have suppressive effects on vasopressin-induced DNA synthesis of rat aortic smooth muscle cells through cAMP production (Murase et al., J. Hypertens., 10 (1992) 1505; Oiso et al., Biochem. Cell. Biol., 71 (1993) 156). In the present study, we investigated the effect of glucocorticoid on cAMP production induced by PACAP, PGE2 and carbacyclin in aortic smooth muscle cells. The pretreatment with dexamethasone significantly inhibited cAMP accumulation induced by these vasoactive agents in a dose dependent manner in the range between 10 pM and 10 nM. These inhibitory effects of dexamethasone were dependent on the time of pretreatment up to 8 h. Dexamethasone inhibited cAMP accumulation induced by NaF, a GTP-binding protein activator, and forskolin which directly activates adenylate cyclase. Moreover, forskolin-induced adenylate cyclase activity was significantly reduced in membranes prepared from the cells treated with dexamethasone. These results strongly suggest that glucocorticoid inhibits cAMP production induced by vasoactive agents in primary cultured rat aortic smooth muscle cells and the inhibitory effect is exerted at the level of adenylate cyclase.
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PMID:Glucocorticoid inhibits cAMP production induced by vasoactive agents in aortic smooth muscle cells. 785 72

Angiotensin-converting enzyme (ACE) activity plays a central role in vessel growth and remodeling as shown by the fact that ACE inhibitors reduce neointimal proliferation after rat carotid injury. To investigate the mechanisms that regulate smooth muscle cell ACE expression, we studied the effects of steroids on ACE activity and mRNA in cultured rat aortic smooth muscle cells. ACE activity was present at low levels independent of growth state. In response to the glucocorticoid dexamethasone (100 nmol/L for 72 hours), ACE activity (hydrolysis of [3H]benzoyl-Phe-Ala-Pro) increased 10.1 +/- 3.1-fold. The increase in activity occurred within 12 hours and peaked after 72 hours of treatment. The increase in ACE activity was specific for glucocorticoids and paralleled their potency (dexamethasone > hydrocortisone = prednisolone). Dexamethasone increased the steady-state level of ACE mRNA in a concentration-dependent manner (21.4 +/- 0.4-fold at 100 nmol/L for 72 hours). Dexamethasone stimulation of ACE expression appeared to be due to both increased transcription and stabilization of ACE enzyme mRNA. This was suggested by the finding that dexamethasone stimulated nuclear run-on expression of ACE mRNA by only threefold, in contrast to the 21-fold increase in steady-state mRNA. These findings establish that ACE is a dynamically regulated enzyme in rat aortic smooth muscle cells. In addition, the present findings suggest an important role for stress steroids in the vascular response to injury in vivo.
Hypertension 1995 Mar
PMID:Glucocorticoids induce angiotensin-converting enzyme expression in vascular smooth muscle. 787 59


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