E. Pamies

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

Background Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. Objectives To elucidate the antioxidant effect of simvastatin. Methods We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Results Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. Conclusions Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Genotype of the CYBA promoter -930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: an observational study.

BACKGROUND AND OBJECTIVE Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). MATERIAL AND METHODS We studied the -930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). RESULTS The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE (P=0.03). A higher frequency of epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes of APOE was observed in patients with PE or NPH compared with controls (P<0.01). There were no significant differences detected in genotype or allele distribution of the MTHFR, C677T polymorphism. APOE epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes had a worse lipoprotein profile characterized by higher plasma values of total cholesterol (P<0.05) and triglycerides (P<0.005). Despite no differences in MTHFR C677T polymorphism distribution, higher levels of plasma homocysteine were observed in patients with PE than in patients with NPH or controls. CONCLUSIONS CYBA and APOE polymorphism showed a different distribution in the groups studied, while no differences were observed in MTHFR C677T polymorphism. APOE genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing's syndrome.

We hypothesized that in nonectopic Cushing syndrome there is an insufficient activity of type II (renal) 11β-hydroxysteroid dehydrogenase (11β-HSD2) that is related to cortisol excess, rather than to corticotropin (adrenocorticotropic hormone [ACTH]) levels. We measured plasma ACTH and urinary-free cortisol (UFF), urinary-free cortisone (UFE), tetrahydrocortisol (UTHF), and tetrahydrocortisone (UTHE) in 24-h urine samples of 24 healthy subjects and 15 patients diagnosed with nonectopic Cushing syndrome. Then, in the group of patients, a new 24-h urine sample was collected after treatment with 800 mg daily of ketoconazole. The UFF/UFE and UTHF/UTHE ratios were calculated as an estimation of 11β-HSD2 activity. The patients had an increase in both the UFF/UFE (19.95±10.3 vs 5.78±4.72 nmol/24 h; p<0.0001) and UTHF/UTHE ratios (5.36±5.23 vs 1.39±0.95 nmol/24 h; p<0.001). Both UFF/UFE and UTHF/UTHE ratios decreased after ketoconazole treatment (19.95±10.3 vs 12.2±6.9 nmol/24 h; p<0.005; and 5.36±5.23 vs 1.62 vs 1.21 nmol/24 h; p<0.001, respectively). The control subjects had a significant relationship between UFF and UFE (r=0.70, p<0.0001), and between UTHF and UTHE (r=0.75, p<0.0001) that did not exist in the patient group. After ketoconazole treatment, the decrease in cortisol excretion in the patient group allowed a positive and significant relation between UFF and UFE (r=0.64, p<0.01) and between UTHF and UTHE (r=0.56, p<0.05) to appear. There was not any significant relationship between either UFF/UFE or UTHF/UTHE ratios and plasma levels of ACTH.

Ambulatory blood pressure monitoring in physicians working in a hospital: is there an increase in the number of subjects with high workplace blood pressures?

Sixty-two physicians from our hospital who were normotensives, as supported by casual blood pressure measurements, underwent 24-h blood pressure monitoring which included their normal work, home rest and sleep periods. During working hours, 19% of the subjects showed mean diastolic and/or diastolic plus systolic blood pressures higher than those admitted as normal by the WHO for casual measurements for out of work subjects. Both mean systolic and diastolic blood pressure measurements, during the work at the hospital, were significantly higher in males (P < 0.01 and P < 0.005, respectively) than the mean of the readings obtained during the 24-h period, but this phenomenon did not occur among the females. Males mean systolic (129.8 +/- 10.6 vs. 117.1 +/- 9.7 mmHg, P < 0.0001) and diastolic pressures (83.4 +/- 8 vs. 74.9 +/- 7.3 mmHg, P < 0.001) were significantly higher during the working period in relation to those of the female group. Discussing the influence of the kind of work on blood pressure, we came to the conclusion of the existence in our environment of a group of subjects (generally males), presenting high blood pressure values during their working period at the hospital and normal or borderline values during the rest of the day. This should be of interest, since it has been reported that subjects with high workplace blood pressure have an increased risk of hypertension and target-organ damage.

Prevalencia de dislipemia y de sus distintos fenotipos en la hipertensión arterial esencial de comienzo reciente

BACKGROUND: To know the prevalence of phenotypic dyslipidemias and their clinical and metabolic characteristics in recently diagnosed hypertensive patients. METHODS: Consecutive study of 158 essential hypertensive patients without previous pharmacological treatment. RESULTS: 69.6% of the patients had some kind of dyslipidemia, being the isolated increase of Lp(a) (27.3%) the most prevalent and the hyperapobetalipoproteinemia the less (10.0%). Age, sex, smoking, alcohol consumption, uric acid, systolic and pulse pressure and serum glucose were different among phenotypes. CONCLUSIONS: Essential hypertensive patients have high and heterogeneous prevalence of dyslipidemias.

Gordon's syndrome: increased maximal rate of the Na-K-Cl cotransport and erythrocyte membrane replacement of sphingomyelin by phosphatidylethanolamine.

Objective Gordons syndrome comprises hypertension, hyperchloremic acidemia, hyperkalemia and intact renal function. We hypothesize that disturbances of one or more cell membrane ion carriers, handling sodium, chloride and potassium, might be relevant in this disorder and, furthermore, that such disturbances might be related to altered cell membrane composition. Design and methods: In a patient diagnosed with Gordons syndrome, we assessed the kinetics (Km and maximal rate) of four membrane sodium transport systems in sodium-enriched erythrocytes, according to the technique of Garay. We also measured the lipid composition of erythrocyte membrane in this patient and 69 essential hypertensive controls, using the Iatroscan technique. Results: Compared to reference values of patients with essential hypertension, this patient exhibited a marked increase in the maximal rate of the Na+−K+−2Cl− cotransport (964.0 μmol/l per cell versus the 391.6 + 222 μmol/l per cell in essential hypertensives). Also, there was an increased concentration of erythrocyte membrane phospatidylethanolamine and a reduced concentration of sphingomyelin (27.9 and 11.1% versus 17.9 ± 3.8% and 18.2 ± 3.4%, respectively). Conclusions: We conclude that this abnormality in membrane Na+−K+−2Cl− cotransport could be responsible for the hyperkalemia, hyperchloremic acidemia and increased reabsorption of sodium observed in this condition and, furthermore, that such disturbance in membrane cotransport might be related to altered phospholipid concentration in cell membranes.

Description of a new quotient that may differentiate blood pressure profiles in essential versus Cushing’s syndrome-related hypertension

Since the presence or absence of a nocturnal decrease in blood pressure values (BP) may suggest an increased risk of visceral complications or the existence of secondary hypertension, several methods have been described for evaluating the BP profile. Nevertheless, a universally accepted system to evaluate this item has not yet been established. Our aim in this study was to test different dispersion quotients (DQ) which estimate the differences between the mean of each hour, and the mean of all the readings in the 24 h period. These quotients may be employed regarding systolic (SBP) or diastolic (DBP) blood pressure, and may be referred to the whole period of 24 h, or to the subperiods morning (m), afternoon (a) or night (n). We have studied two non selected groups of essential (n=20) or secondary (Cushing’s syndrome, n=17) hypertensives. We observed a marked decrease in these quotients, particularly DQ-SBP and nDQ-SBP, in secondary hypertensives (respectively 10.2±2.9 vs 15.6±4.2 and 11.8±5.0 vs 20.5±6.3, p<0.0001), thus indicating, a blunted nocturnal fall of BP in these patients. Also the DQ and particularly DQ-SBP, nDQ-SBP and nDQ-DBP, showed a high positive and negative predictive value, sensitivity and specificity for pertaining to the Cushing’s syndrome group (respectively: 0.75, 0.88, 0.88, 0.75; 0.86, 0.82, 0.77 0,90; and 0.78, 0.84, 0.82, 0.80).