Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. 11 beta-Hydroxysteroid dehydrogenase converts cortisol to inactive cortisone in man. In distal renal tubules, this inactivation protects mineralocorticoid receptors from cortisol. Congenital 11 beta-hydroxysteroid dehydrogenase deficiency and inhibition of 11 beta-hydroxysteroid dehydrogenase by liquorice or carbenoxolone result in cortisol-dependent hypokalaemia and hypertension. 2. 11 beta-Hydroxysteroid dehydrogenase is expressed in vascular smooth muscle. Both glucocorticoids and mineralocorticoids potentiate vascular responses to noradrenaline. 11 beta-Hydroxysteroid dehydrogenase activity may therefore influence vascular tone. 3. Experiments were performed in healthy subjects with and without 7 days of oral administration of 11 beta-hydroxysteroid dehydrogenase inhibitors (liquorice or carbenoxolone), and in a patient with congenital 11 beta-hydroxysteroid dehydrogenase deficiency. We measured the following parameters: dermal vasoconstriction after topical application of cortisol, forearm blood flow during brachial artery infusion of cortisol or noradrenaline, and blood pressure during systemic infusion of noradrenaline. 4. Cortisol-induced dermal vasoconstriction was increased by liquorice (23 +/- 6 to 52 +/- 7 units; P < 0.04) and in congenital 11 beta-hydroxysteroid dehydrogenase deficiency (87 units). In congenital 11 beta-hydroxysteroid dehydrogenase deficiency intraarterial infusion of cortisol caused vasoconstriction (20% reduction in blood flow in the infused arm) and accentuated the response to application of lower-body negative pressure, which stimulates sympathetically mediated vasoconstriction (35% reduction). However, intra-arterial infusion of cortisol had no effect in healthy subjects either with or without administration of liquorice. 5. Carbenoxolone potentiated both noradrenaline induced forearm vasoconstriction (P < 0.01) and pressor response (P < 0.001). 6. We conclude that 11 beta-hydroxysteroid dehydrogenase modulates the access of cortisol to vascular receptors and thereby influences vascular sensitivity to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoids and blood pressure: a role for the cortisol/cortisone shuttle in the control of vascular tone in man. 132 32

Carbenoxolone Sodium (CS), a chemical derivative of liquorice is known to be associated with hypertension, increased sodium retention and hypokalemia. The present studies describe the effects of CS on the renal actions of the glucocorticoids Corticosterone (B) and Cortisol (F) on sodium and potassium in adrenalectomized male rats. B (50, 100 and 500 micrograms/rat) and F (1 mg/rat) were found to possess no intrinsic antinatriuretic activity which is represented by a decrease in the Na+ to creatinine ratio; while only B (500 micrograms/rat) demonstrated kaliuretic effects as indicated by an increase in K+ to creatinine ratios. B and F showed very significant antinatriuretic and kaliuretic properties following pretreatment with CS (2.5 mg/rat). CS alone was not found to be antinatriuretic at this dosage. Further experiments demonstrated that lower dosages of CS (500 and 1,000 micrograms/rat) also cause B to exhibit Na+ retaining and K+ excreting properties. Thus, we have demonstrated that pretreatment with CS can confer mineralocorticoid-like activity upon the glucocorticoids B and F.
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PMID:The antinatriuretic and kaliuretic effects of the glucocorticoids corticosterone and cortisol following pretreatment with carbenoxolone sodium (a liquorice derivative) in the adrenalectomized rat. 291 28

The circulatory effects of oleanoic acid sodium hydrogen succinate (OSS), an analogue of the anti-ulcer drug, carbenoxolone, were investigated. As carbenoxolone produces such adverse effects as sodium retention and a subsequent elevation of the arterial blood pressure in man, the present study was aimed at determining whether OSS is similar or different from it in this respect. Carbenoxolone, (43,3 mg/kg po) and OSS (66,6 mg/kg po) were given to rats twice daily for 4 weeks. The systolic blood pressure was elevated already after the first week of treatment. The hypertension was accompanied by bradycardia, which increased with the time of treatment. In the blood an increase in the creatinine level, a decrease in the urea level, and a slight elevation in sodium concentration were found after the treatment, while the potassium concentration during the whole treatment period (4 weeks) remained unchanged. Although the principal aldosterone-like effects of carbenoxolone were attributed to the oxygen presence in position 11 of the glycyrrhetinic acid ring, [8], the absence of an oxygen at that position in OSS did not cause the loss of the adverse circulatory effect.
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PMID:Cardiovascular action of a new carbenoxolone derivative. 324 64

Between 1970 and 1979, 140 patients aged between 19 and 84 years with endoscopically confirmed gastric ulcer (GU), were treated with Biogastrone in reducing doses for 6 months. They received a daily dose of 300 mg for one week, 150 mg for 5 weeks, 100 mg for 6 weeks and 50 mg for the remainder of the 6 months. All the patients were reviewed at 2, 4, 6, 8, 12, 16, 20, 32, and 38 weeks and thereafter every 3 months or earlier in the event of significant dyspepsia. The anticipated recurrence rate of GU of approximately 42% at 2 years (3) was nearly halved to 26.7% over a median follow-up of 36 months in 140 cases completing the full six months course of treatment. The incidence of side effects was as follows: (i) A weight gain of 3.5 kg or more was seen in 23% of the patients at 2 weeks; this effect was maintained through the 6 month period. (ii) Oedema was noted in 14% of the patients at 2 weeks but declined to a 2% incidence by the end of the study. (iii) Elevated diastolic blood pressure in 14--18% of patients below 60 years and 20--27% patients above 60 years of age was noted throughout the study period. A high proportion of patients (38%) receiving other therapy had hypertension prior to the trial period; Carbenoxolone treatment had little further effect on blood pressure in these patients. (iv) Hypokalaemia was noted in the early stages of treatment especially in those over 60 years (43%). The incidence declined with the reduction in dosage through the 6 month treatment period. All side effects were successfully treated by diuretics and potassium supplements.
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PMID:Long-term therapy with carbenoxolone in the prevention of recurrence of gastric ulcer. Natural history and evolution of important side-effects and measures to avoid them. 693 41

Carbenoxolone inhibits the enzyme complex 11 beta-hydroxysteroid dehydrogenase. Functional deficiency of this complex might contribute to the hypertension of renal parenchymal disease. We have compared the effects of carbenoxolone (300 mg/day for 5 days) in six normal subjects and seven patients with renal disease. Patients with renal disease had higher blood pressure, plasma creatinine concentration (0.15 +/- 0.01 mmol/L cf. 0.09 +/- 0.01 mmol/L) and urine protein excretion than normals. In normal subjects carbenoxolone increased body weight and plasma chloride and decreased initial urine sodium excretion, packed cell volume, plasma albumin, renin and aldosterone concentrations. In patients with renal disease, carbenoxolone also produced these effects, but in addition significantly increased systolic, (129 +/- 3 to 135 +/- 5 mm Hg) mean (97 +/- 3 to 101 +/- 3 mm Hg) and diastolic blood pressure (81 +/- 3 to 85 +/- 2 mm Hg) and lowered plasma potassium (4.1 +/- 0.1 to 3.8 +/- 0.1 mmol/L) and urine sodium:potassium ratio (1.57 +/- 0.22 to 2.60 +/- 0.54). These results are consistent with the notion that partial deficiency of 11 beta-hydroxysteroid dehydrogenase contributes to the hypertension of renal parenchymal disease.
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PMID:Haemodynamic and metabolic effects of carbenoxolone in normal subjects and patients with renal impairment. 792 Apr 54

Carbenoxolone causes hypertension indirectly by inhibition of 11beta-hydroxysteroid dehydrogenase and consequent elevation of intracellular glucocorticoid levels and enhancement of vasoconstrictor action. We performed the present study to determine whether carbenoxolone also enhances vascular tone directly by mechanisms independent of glucocorticoids and other systemic influences. Exposure of rat aortic rings to 10 to 100 micromol/L carbenoxolone in aerated Krebs-Henseleit buffer for 24 hours resulted in concentration-dependent increases in angiotensin II (Ang II) (100 nmol/L)-stimulated contractions and significant shifting of the phenylephrine cumulative contraction curve to the left but not increases in KCI (120 mmol/L)-stimulated contractions. Maximal enhancement of Ang II contraction was 39 percent. In contrast, brief (15-minute) exposure to 100 micromol/L carbenoxolone did not alter Ang II contractions. Mechanical denudation of the endothelium obviated enhancement of Ang II contractions by carbenoxolone, suggesting interaction of carbenoxolone with the endothelium. Endothelium-dependent relaxation of precontracted rings to acetylcholine or ATP was reduced by more than 90 percent by 24-hour pretreatment with 100 micromol/L carbenoxolone but not with 100 micromol/L deoxycorticosterone acetate (a mineralocorticoid) or 100 mu mol/L glycyrrhizic acid (a natural 11beta-hydroxysteroid dehydrogenase inhibitor). Vascular smooth muscle relaxation with sodium nitroprusside was not inhibited by carbenoxolone. Incubation of cultured endothelial cells with 100 mu mol/L carbenoxolone for 24 hours did not inhibit nitric oxide synthase activity, as measured by conversion of [3H]L-arginine to [3H]L-citrulline. Electron micrography demonstrated that endothelial cell ultrastructure but not vascular smooth muscle cell ultrastructure was abnormal after incubation of rings for 24 hours with 100 micromol/L carbenoxolone. These studies suggest that carbenoxolone concentrations higher than 10 micromol/L enhance vasoconstrictor action via selective toxicity to the endothelium and elimination of endothelium-dependent relaxation.
Hypertension 1996 Jun
PMID:Carbenoxolone damages endothelium and enhances vasoconstrictor action in aortic rings. 864 47