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A Soro

Publications and source records attributed to A Soro.

At least 19 recordsLinked to original sources

Low HDL cholesterol concentration is associated with increased intima-media thickness independent of arterial stiffness in healthy subjects from families with low HDL cholesterol.

BACKGROUND: Low high-density lipoprotein cholesterol (HDL-C) is associated with increased risk for developing coronary artery disease. Cardiovascular disease is characterized by increased intima-media thickness (IMT) and arterial stiffness, but the effect of low HDL on these measurements has not been reported. MATERIALS AND METHODS: We studied 18 apparently healthy subjects from families with low HDL-C and 18 control subjects, which were pair-matched to maximize statistical power. Intima-media thickness was assessed using ultrasound examination of the carotid arteries. Arterial stiffness was measured using applanation tonometry on the radial artery and pulse-wave analysis to obtain central aortic pulse-pressure waveform, from which the augmentation index, a measure of global large artery stiffness, was calculated. RESULTS: Low HDL subjects (age 41 +/- 3 years, BMI 26.6 +/- 1.0 kg m(-2) had significantly lower HDL-C than the control subjects (age 41 +/- 3 years, BMI 26.5 +/- 1.0 kg m-2; 1.00 +/- 0.05 vs. 1.49 +/- 0.09 mmol L-1, low HDL vs. control subjects, P < 0.0001). Subjects with low HDL-C had significantly thicker mean IMTs than the control subjects (0.77 +/- 0.03 vs. 0.70 +/- 0.02 mm, low HDL vs. control subjects, P < 0.01). The maximal (0.99 +/- 0.04 vs. 0.89 +/- 0.03 mm, P < 0.01), far wall (0.76 +/- 0.04 vs. 0.69 +/- 0.02 mm, P < 0.05) and carotid bulb (1.11 +/- 0.06 vs. 0.97 +/- 0.04 mm) IMTs were also significantly increased, whereas the mean common carotid and the internal artery IMT were not. The age-related increase in mean IMT was more pronounced in the low HDL subjects than the control subjects (P < 0.01 for difference between elevations of age vs. IMT slopes). There were no differences in central pressure augmentation, the augmentation index, peripheral or central blood pressures between the groups. CONCLUSIONS: A low HDL-C concentration is associated with thickening of carotid IMT independent of other risk factors in healthy affected members of low HDL families.

Adult↗

Interaction of alpha(1)-Na,K-ATPase and Na,K,2Cl-cotransporter genes in human essential hypertension.

Essential hypertension is a common disease the genetic determinants of which have been difficult to unravel because of its clinical heterogeneity and complex, multifactorial, polygenic etiology. Based on our observations that alpha(1)-Na,K-ATPase (ATP1A1) and renal-specific, bumetanide-sensitive Na,K,2Cl-cotransporter (NKCC2) genes interactively increase susceptibility to hypertension in the Dahl salt-sensitive hypertensive (Dahl S) rat model, we investigated whether parallel molecular genetic mechanisms might exist in human essential hypertension in a relatively genetic homogeneous cohort in northern Sardinia. Putative ATP1A1-NKCC2 gene interaction was tested by comparing hypertensive patients (blood pressure [BP] >165/95 mm Hg) with normotensive controls age >60 years with BP <140/85 mm Hg. Genotype analysis with microsatellite markers revealed conformation to Hardy-Weinberg proportions for 6 alleles of both ATP1A1 (D1S453) and NKCC2 (NKCGT7) markers, respectively. Two-by-six chi(2) analysis of alleles identified overrepresentation of ATP1A1 No. 4 and NKCC2 No. 4 alleles, respectively, in hypertensives compared with controls. With a qualitative trait framework, single-gene analysis detected association of both the ATP1A1 No. 4 allele (P=0.004, chi(2)=8.094, df=1) and the NKCC2 No. 4 allele (P=0.0002, chi(2)=14.279, df=1) with moderate to severe hypertension. Digenic analysis revealed that ATP1A1 No. 4-NKCC2 No. 4 allele interaction increases susceptibility to hypertension (P<0.0001, chi(2)=22.3, df=1) beyond levels obtained in single-gene analysis. Analysis was also performed in a quantitative trait framework with BP as the continuous trait parameter. Digenic analysis of ATP1A1 No. 4-NKCC2 No. 4 allele interaction revealed significant association with systolic (1-way ANOVA, P=0.000076) and diastolic (P=0.00099) BP. Interaction was corroborated by 2x2 factorial ANOVA for interaction (systolic BP interaction term, P<0.05, diastolic BP interaction term, P=0.035). The data are compelling that ATP1A1 and NKCC2 genes are candidate interacting hypertension-susceptibility loci in human essential hypertension and affirm gene interaction as an important genetic mechanism underlying hypertension susceptibility. Although corroboration in other cohorts and identification of functionally significant mutations are imperative next steps, the data provide a genotype-stratification scheme, with 4-fold predictive value (odds ratio, 4.28; 95% confidence interval, 2.29 to 8.0), which could help decipher the complex genetics of essential hypertension.

Adult↗

Absence of D147E mutation of CYP11B2 gene in hypertensive patients with increased corticosterone and aldosterone production.

OBJECTIVE: 11beta-Hydroxylase and aldosterone synthase are two highly homologous genes involved in different forms of human hypertension and in different animal models of hypertension. It has been shown that the conservative substitution D147E in the human CYP11B2 gene results in an increased production of corticosterone and aldosterone in vitro. A gene conversion between the CYP11B1 and CYP11B2 genes could be responsible for such a substitution. METHODS: In this study we investigated the presence of the mutation D147E of CYP11B2 in a group of 128 patients with primary aldosteronism, 68 patients with essential hypertension and increased corticosterone production and in 48 normal volunteers. RESULTS AND CONCLUSIONS: We did not identify any patient carrying this mutation, indicating that if it exists it is very rare and so has no relevance in determining the increased steroid excretion seen in some subtypes of human hypertension.

Aged↗

High plasma prorenin in non diabetic siblings of non insulin-dependent diabetes mellitus patients.

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1. the levels of plasma prorenin in non affected siblings of NIDDM probands as opposed to normal subjects without family history of diabetes, and 2. whether plasma prorenin raises in parallel to urinary protein loss in NIDDM patients. Prorenin (solid-phase trypsin) and micro-macroalbuminuria (radioimmunoassay) were evaluated. Plasma prorenin was higher in NIDDM probands and siblings than in non NIDDM siblings (37+/-31 vs. 25+/-15 ng/ml/h, p<0.0005) who, in turn, showed higher plasma prorenin than non diabetic controls without family history of diabetes (25+/-15 vs. 17+/-8 ng/ml/h, p<0.005). Plasma prorenin was higher in NIDDM siblings of micro-macroalbuminuric probands than in NIDDM siblings of non micro-macroalbuminuric probands (40+/-26 vs. 29+/-20 ng/ml/h, mean +/- SD, p = 0.0058) whereas no difference was found among non diabetic siblings (24+/-14 vs. 22+/-11 ng/ml/h, NS). Our data confirm that plasma prorenin is elevated in NIDDM patients, and show: 1. that the raise of plasma prorenin in non-NIDDM siblings of a diabetic patient does not depend entirely from the presence of diabetes, and 2. that plasma prorenin in NIDDM probands and their concordant siblings goes along with micro-macroalbuminuria.

Blood Pressure↗

The role of alpha-adducin polymorphism in blood pressure and sodium handling regulation may not be excluded by a negative association study.

The basic requirement for declaring an association study positive is that the "hypertension-favoring" allele is more frequent in hypertensive cases than in normotensive controls. However, both positive and negative associations with hypertension have been found for the same polymorphism when studied in different populations. In the present study, we addressed the question of the possible cause(s) of this discrepancy among populations by using the alpha-adducin polymorphism as a paradigm. Four hundred ninety hypertensives and 176 normotensives enrolled in Sassari, Italy, and 468 hypertensives and 181 normotensives enrolled in Milano, Italy, were genotyped for the alpha-adducin Gly460Trp polymorphism. The blood pressure response to 2 months of hydrochlorothiazide therapy could be evaluated in 143 (85 in Sassari and 58 in Milano) hypertensives with and without the 460Trp alpha-adducin allele. The alpha-adducin 460Trp allele was not significantly more frequent in hypertensives in the Sassari population but was more frequent in hypertensives than in normotensives in Milano (P=0.019). Basal plasma renin activity was lower and blood pressure fall after diuretic therapy more pronounced (P<0.01) in hypertensives carrying at least one 460Trp allele than in Gly460Gly homozygotes, irrespective of their membership in the Sassari or Milano cohort. The effect of alpha-adducin genotype in predicting basal plasma renin activity and blood pressure decrease with diuretic treatment is similar in Sassari and Milano, despite the lack of association of the alpha-adducin genotype with hypertension in Sassari.

Aged↗

Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia.

Certain hydroxymethylglutaryl coenzyme A reductase inhibitors, ie, statins, may cause vasodilation by restoring the endothelial dysfunction that frequently accompanies hypertension and hypercholesterolemia. Several studies have found that a blood pressure reduction is associated with the use of statins, but conclusive evidence from controlled trials is lacking. After an 8-week placebo and diet run-in period, 30 persons with moderate hypercholesterolemia and untreated hypertension (total cholesterol 6.29+/-0.52 mmol/L, systolic and diastolic blood pressure 149+/-6 and 97+/-2 mm Hg) were randomized in a double-blind manner to placebo or pravastatin (20 to 40 mg/d) in a crossover design. In 25 participants who completed the 32-week trial, pravastatin decreased total and LDL cholesterol (both -1.09 mmol/L, P=0.001), systolic and diastolic blood pressure (-8 and -5 mm Hg, both P=0.001), and pulse pressure (-3 mm Hg, P=0.011) and blunted the blood pressure increase caused by the cold pressor test (-4 mm Hg, P=0.005) compared with placebo. It also reduced the level of circulating endothelin-1 (P=0.001). The blood pressure results were virtually unchanged in stratified analyses according to gender and age and in intention-to-treat analyses that included the 5 patients who dropped out of the study. When the participants were taking either placebo or pravastatin, blood pressure was not significantly correlated with total or LDL cholesterol or with circulating endothelin-1. Pravastatin decreases systolic, diastolic, and pulse pressures in persons with moderate hypercholesterolemia and hypertension. This antihypertensive effect may contribute to the documented health benefits of certain statins.

Adult↗

[Postoperative follow-up of type A aortic dissectionexperience with 67 patients].

BACKGROUND: The surgical treatment of type A aortic dissection is usually palliative and most surviving patients remain at considerable risk to develop late postoperative complications; consequently, there is the need for careful long-term follow-up. The present study reports on our experience in the postoperative follow-up of a consecutive series of patients with type A aortic dissection. METHODS: Between January 1986 and December 1996, 89 patients underwent emergency surgery for type A acute aortic dissection; the overall hospital mortality rate was 22% (20/89). This study includes the 69 hospital survivors (49 men and 20 women). Forty-six patients had ascending aortic graft replacement, 13 patients underwent replacement of aortic valve and ascending aorta by a composite graft. The surgical repair was extended to the aortic arch in 5 patients. All patients were serially evaluated by clinical examination and imaging techniques (transthoracic echocardiography in all patients, magnetic resonance imaging in 40, transesophageal echocardiography in 33 and computed tomography in 25). Follow-up was complete in 97% of patients (two patients were lost to follow-up and excluded from the study) and extended to a maximum of 152 months (mean 74 +/- 39 months). The postoperative quality of life was assessed by a questionnaire in 51 current survivors. Risk factors for cardiovascular death, reoperation and poor quality of life were investigated with univariate and multivariate analysis. RESULTS: During the follow-up period 15 patients (22%) died; in 13 cases death was due to cardiovascular causes and in 6 of them it was related to aortic disease. The Kaplan-Meier survival was 92 +/- 3%, 87 +/- 5%, 78 +/- 6% and 70 +/- 8% at 2, 4, 6 and 8 years, respectively. A persistent aortic dissection was demonstrated in 50 patients (75%) and 42 of them showed the presence of flow in the false lumen. A dilatation of one or more aortic segments was found in 59 patients (88%), with a diameter > or = 50 mm in 17 and > or = 60 mm in 8. In 30 patients who underwent transesophageal echocardiography the relation between aortic dimensions and flow pattern in the false lumen was examined; the presence of aneurysmal dilatation with a diameter > or = 50 mm was significantly correlated with a "high flow" pattern. Ten patients (15%) underwent reoperation from 13 to 83 months postoperatively. Reoperation was indicated for: sinus of Valsalva aneurysm and severe aortic regurgitation (2 patients), severe aortic regurgitation (2 patients), aneurysm of the arch (1 patient), thoracoabdominal aneurysm (1 patient), periprosthetic pseudoaneurysm (4 patients). The hospital mortality rate was 20% (2 patients). Sixty-two% of current survivors are asymptomatic; 30 patients returned to their predissection status. Quality of live is judged "good" by 23 patients, "fairly good" by 21 patients and "poor" by 7 patients. No significant independent risk factor for cardiovascular death, reoperation and poor quality of life was identified. CONCLUSIONS: The long-term prognosis after surgical treatment of type A aortic dissection is not satisfactory because of a significant risk of late complications. However, the results of our study can be judged fairly good, particularly if we consider the natural history of the disease.

Aged↗

Evaluation of mean right atrial pressure by two-dimensional and Doppler echocardiography in patients with cardiac disease.

BACKGROUND: Several approaches have been used for noninvasive estimation of right atrial pressure (RAP), but, no currently available method has gained any definite validation. The purpose of this study was to evaluate the accuracy of two-dimensional and Doppler echocardiography in estimating mean RAP in patients with cardiac disease. METHODS: We examined the relation of mean RAP to right atrial size and function, size and respiratory changes of inferior vena cava and Doppler parameters of tricuspid and hepatic vein flow in 114 consecutive patients (77 men, 37 women; mean age 57 +/- 12 years) with various cardiac diseases undergoing cardiac catheterization. Echocardiographic studies were performed within 24 hours before catheterization (mean interval 6 +/- 3 hours). Patients were assigned to 3 groups according to the values of mean RAP (group 1, < or = 8 mmHg; group 2, between 9 and 12 mmHg; group 3, > 12 mmHg). RESULTS: Mean RAP ranged from 3 to 20 mmHg (mean 9.1 +/- 4.3 mmHg). It correlated most strongly with the collapsibility index of inferior vena cava (IVCCI) (r = -0.76), minimal inspiratory diameter of inferior vena cava (r = 0.72) and deceleration time of early tricuspid flow (DT) (r = -0.61). Discriminant analysis demonstrated that IVCCI and DT were major determinants of mean RAP with 81.6% of cases correctly assigned to study groups: 96% of patients of group 1 and 87% of patients of group 3 were identified, whereas the accuracy in identifying the patients of group 2 was lower (46%). An IVCCI > 45% was the best cutoff point in predicting a mean RAP < or = 8 mmHg; an IVCCI < 35% and a DT < 150 msec were the best cutoff points in predicting a mean RAP > or = 15 mmHg. The best multivariate equation predicting mean RAP was: mean RAP = 23.3 - 0.2 IVCCI -0.026 DT (r = 0.80, R2 = 0.64). This equation was 81% sensitive and 84% specific in detecting a mean RAP < or = 8 mmHg and 74% sensitive and 97% specific in detecting a mean RAP > 12 mmHg. CONCLUSIONS: Mean RAP can be estimated noninvasively by two-dimensional and Doppler echocardiography. The combined analysis of IVCCI and DT provides an accurate prediction on mean RAP < or = 8 mmHg and > 12 mmHg, whereas the prediction of intermediate values is less accurate.

Adult↗

[Deglutition in patients treated with reconstructive laryngectomy].

INTRODUCTION: We stress the importance of dynamic radiologic studies of swallowing in the patients submitted to reconstructive laryngectomy. MATERIAL AND METHODS: January, 1989, to December, 1996, we examined 36 patients submitted to reconstructive laryngectomy, namely cricohyoidoepiglottopexy in 34 cases, cricohyoidopexy in 1 case and Guerrier's cricohyoidoepiglottopexy in 1 case. Dynamic radiologic studies were performed with fluoroscopic videorecording (Sony U-Matic RM 580) from an X-ray unit. The study was performed with the patients standing or sitting, initially acquiring AP and LL fluoroscopic images of the oropharyngeal region at rest and during swallowing. The patients then swallowed 2 boluses of 5 ml liquid (60%) and semiliquid (250%) barium. When aspiration was suspected, we began with a 2-ml bolus. RESULTS: The patients were grouped by symptoms: group A patients had no symptoms, group B patients had dysphagia and group C patients presented aspiration. The functional changes were: reduced pharyngeal contraction, reduced epiglottis deflection, reduced hyoid bone elevation, aspiration, altered upper esophageal sphincter function. The organic alterations were: parapharyngeal diverticulum, pharyngeal stenosis, posterior pharyngeal wall introflexion. Three group A patients had severe posterior pharyngeal wall introflexion, 4 had marked retention and 2 of them presented postswallowing aspiration. Two group B patients had major retention, 1 cricopharyngeal incoordination, 3 posterior pharyngeal wall introflexion, 2 a pseudodiverticulum and 2 a luminal stenosis. Seven group C patients had intraswallowing and 3 postswallowing aspiration. CONCLUSION: The videofluorographic identification of organic and functional complications, sometimes unknown in asymptomatic patients, is useful for therapy and suggests the speech specialist the best compensatory mechanism to improve the patients' swallowing and consequently their quality of life. Moreover, videofluorography of swallowing is a very useful tool in the follow-up, to monitor treatment outcome after rehabilitation.

Deglutition↗

In vivo and in vitro effects of carbenoxolone on glucocorticoid receptor binding and glucocorticoid activity.

Carbenoxolone potentiates the mineralocorticoid activity of endogenous glucocorticoid hormones by inhibiting the enzyme 11 beta-hydroxysteroid dehydrogenase, which converts cortisol and corticosterone to inactive 11-oxo-derivatives. We addressed the question of whether glucocorticoid activity is also affected by carbenoxolone. Using a rat model involving low dose corticosterone treatment, we found that carbenoxolone neither potentiated nor inhibited the modest increases in blood pressure or reductions in weight gain caused by steroid treatment. Other indices of glucocorticoid activity including white blood cell number, thymus weight, and down regulation of the glucocorticoid receptor were unaffected. In vitro studies with liver and kidney cytosol preparations indicated that carbenoxolone did compete for 3H-dexamethasone binding sites. Carbenoxolone was 5-10 times more effective than glycyrrhetinic acid, 20-30 thousand times less effective than dexamethasone, and is therefore, approximately 1000 times less effective than corticosterone. Analysis of dexamethasone-binding curves indicated a single class of receptor. We conclude that carbenoxolone at the dose tested does not have intrinsic glucocorticoid activity in vivo, nor does it modulate the activities of corticosterone. Carbenoxolone binds weakly to the glucocorticoid receptor. It is not clear whether this weak affinity accounts for some or any of the direct in vitro effects of high concentrations of carbenoxolone that others have described.

Animals↗

11 beta-Hydroxylase activity in glucocorticoid suppressible hyperaldosteronism: lessons for essential hypertension?

Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.

Adrenocorticotropic Hormone↗

[Computerized tomography and magnetic resonance in the diagnosis of recurrent rectal neoplasms: comparison of reliability and errors of both methods].

Our work was aimed at assessing the accuracy of CT and MRI in the early identification of postoperative recurrences of rectosigmoid cancer, quantifying false positive and false negative ratios and questionable findings. A homogeneous series of 50 patients submitted to surgery for primary rectosigmoid carcinoma was studied with both CT and MRI and followed-up for up to 2 years: local recurrences were observed in 15 patients (30%) which occurred within the first year of surgery in 67% of cases and were in extraluminal site in 86% of cases. CT appeared to be a reliable and highly sensitive screening method, with 82% sensitivity: only 2 false negatives were observed, which were nevertheless followed-up because CT had yielded questionable, and not negative, findings. In contrast, CT had only 78% specificity, being unable to differentiate fibrosis, displaced normal structures and recurrences in 7 cases; its positive predictive value (PPV) was 66%, with 89% negative predictive value (NPV) and 80% accuracy. MRI had a complementary role to CT, because of its capabilities in discriminating all the questionable CT cases and in identifying all CT false positives, thanks to its higher specificity (100%). MRI had 74% sensitivity, which was lower than that of CT; MRI yielded 2 false negatives which, however, had been previously diagnosed with CT. MRI had 100% PPV, 89% NPV and 92% accuracy. Therefore, for the early detection of rectal cancer recurrences, the following diagnostic protocol is suggested: CT should be performed first, as a screening method, within 2-4 months of surgery, and repeated every 6-8 months during the first 2 years-together with CEA values monitoring. MRI should be reserved to the patients in whom CT findings were positive, questionable, or in disagreement with clinical symptoms and/or with increasing CEA values. If MRI fails to solve the diagnostic doubt, a CT-guided biopsy of the mass should be performed.

Adenocarcinoma↗

Effects of the glucocorticoid antagonist RU486 in spontaneously hypertensive and Sprague Dawley rats.

The effect of a low dose of the gluco-corticoid receptor antagonist, RU486, was tested in spontaneously hypertensive (SHR) and in Sprague Dawley (SD) rats. In SD rats, RU486 (50 micrograms/day, 18 days) significantly increased growth rate and thymus weight, probably by antagonising the actions of endogenous glucocorticoid hormones. Blood pressure and plasma corticosterone levels were not affected by RU486 at this dose. In leucocytes, RU486 treatment in vivo reduced the number of glucocorticoid binding sites but did not affect binding affinity. In contrast, growth rate and thymus weight were not altered in SHR when treated with the same dose of RU486 for a longer period (60 days). Blood pressure was unaffected as were leucocyte glucocorticoid receptor characteristic. Glucocorticoid receptor binding characteristics for RU486 were similar for liver cytosol of SD and SHR. We conclude that the apparent difference in sensitivity to RU486 between strains is probably not due to differences in interaction of the antagonist with the glucocorticoid receptor but may be caused by differences in pharmacokinetics of RU486 between strains.

Adrenal Glands↗

Recognition of markers of response to potassium-canrenoate in essential hypertension.

Potassium canrenoate (K-Can) prevents hypertension in Milan hypertensive strain (MHS) but not in spontaneously hypertensive rats (SHR). Essential hypertensive patients (HT) may have differential sensitivity to diuretics, since a subgroup of HT insensitive to hydrochlorothiazide (HCTZ) but sensitive to K-Can has previously been found. The aims of this study were: 1) to seek markers of response in essential hypertensive patients selectively sensitive to K-Can: and 2) to test whether selective sensitivity to furosemide may also be demonstrated. After 2 weeks of placebo (P) 50 uncomplicated, mild to moderate HT (46 +/- 9 yrs, mean +/- SD) received K-Can (50 mg/day) for 4 weeks. After 2 more weeks of P, patients received HCTZ (25 mg) and furosemide (25 mg) for 4 weeks each in a single blind crossover design, with 2 weeks P between each treatment. Dosages were doubled after 2 weeks if diastolic blood pressure (DBP) was > 90 mmHg. Responders (R) were those HT whose DBP was < or = 90 mmHg and/or at least 10 mmHg lower than before treatment. Systolic blood pressure (SBP)/DBP was measured every 2 weeks with plasma renin activity (PRA), red blood cell Na(+)-K(+)-Cl- cotransport (COT) and Na(+)-K+ ATPase pump activity measured at the end of the first P period, and serum electrolytes at the end of each period. Four HT dropped out because of low compliance, 6 because of reversible side effects, and 1 because blood pressure was not back to pre-treatment value after the second placebo period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evidence of coexisting changes in 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activity in subjects with untreated essential hypertension.

We compared corticosteroid metabolite excretion rates and patterns in a group of 68 subjects with untreated essential hypertension and a matched group of 48 normotensive control subjects. The ratio of tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone and the ratio of allotetrahydrocortisol to tetrahydrocortisol were significantly higher in the hypertensive group. This is qualitatively similar to the situation found in patients with the syndrome of apparent mineralocorticoid excess or subjects treated with licorice or carbenoxolone where hypertension is known to arise from deficiencies of 11 beta-hydroxysteroid dehydrogenase and 5 beta-reductase activities. The equivalent ratios for corticosterone metabolites were not different between groups, but total corticosterone metabolite excretion was higher in the hypertensive group. Plasma cortisol levels were lower in hypertensive than in control subjects, but corticosterone levels were higher. This evidence supports a previous suggestion that the activities of these two enzymes may be reduced in essential hypertension, but the contribution of these changes to hypertension is not known.

11-beta-Hydroxysteroid Dehydrogenases↗

Mildly raised corticosterone excretion rates in patients with essential hypertension.

In a large group of patients with untreated hypertension, excretion rates of tetrahydrocorticosterone (THB), allotetrahydrocorticosterone (alloTHB) and tetrahydro-11-dehydrocorticosterone (THA) were all significantly higher than in a group of matched normotensive controls. Using the sum of these metabolites as an index of corticosterone secretion rate suggests that this variable is also higher. The increase was small (all excretion rates remained within the normal range) and corticosterone has low glucocorticoid and mineralocorticoid potency calling the clinical significance of this finding into question. However, it is possible that in combination with mildly deficient 11 beta-hydroxysteroid dehydrogenase activity such increases in corticosterone levels might affect blood pressure.

Corticosterone↗