Factores genéticos en la hipertensión arterial / Genetic factors in arterial hypertension

La hipertensión arterial (HTA) resulta de la interacción entre factores genéticos y ambientales. Aunque las bases genéticas de la enfermedad están firmemente establecidas y el desarrollo en el campo de la biología molecular y genética ha sido muy importante en los últimos años, el avance en el conocimiento de las alteraciones genéticas causantes de la HTA no ha sido muy satisfactorio. Se han identificado las mutaciones genéticas responsables de algunas formas raras de hipertensión de origen mendeliano, pero el estudio de los genes posiblemente implicados en la herencia de la HTA (genes candidatos) ha dado en general resultados contradictorios. En esta revisión resumimos los estudios más recientes y significativos realizados sobre los genes candidatos en la HTA (AU)

Renin-angiotensin-aldosterone system and G-protein beta-3 subunit gene polymorphisms in salt-sensitive essential hypertension.

Approximately 50% of hypertensive patients are salt sensitive (they increase their Blood Pressure in response to sodium intake or volume expansion). Mechanisms underlying salt sensitivity are not completely elucidated although there is evidence that they may be genetically determined. The aim of this study is to establish the relation among some genetic polymorphisms of the renin-angiotensin system (RAAS) and the beta-3 subunit of the protein G and salt sensitivity. We studied 102 essential hypertensive patients, stage 1-2 and without target organ damage. Salt sensitivity was assessed by the rapid protocol of Weinberger. We determined by polymerase Chain reaction techniques the following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE), A1166C of the angiotensin II type 1 receptor (AT1R), -344C/T and intron 2 conversion (IC) of the aldosterone synthase (CYP11B2), and C825T of the beta-3 subunit of the protein G (GNB3). 41 patients (40.19%) were salt sensitive. The distribution of the different polymorphisms was similar in both groups of patients, but subjects carriers of the W allele of the CYP11B2 IC polymorphism had a greater risk for salt sensitivity as compared with no carriers (37 of 41, 90.2% vs 4 of 41, 9.8%, OR 3.02, P<0.05). Although there is no association between salt sensitivity and the different studied genotypes of the RAAS and of the GNB3, our data show a greater risk for salt sensitivity among carriers of the W allele of the CYP11B2 1C polymorphism.

Hematoma en psoas / Psoas hematoma

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Hepatitis aguda colostástica como forma de afectación extranodal primaria de un linfoma no Hodgkin

No disponible

Genetic variation in the beta-3-adrenergic receptor in essential hypertension.

We investigated the role of the beta-3-adrenergic receptor polymorphism in membrane lipid composition and erythrocyte membrane sodium transport in essential hypertensive patients. We studied 87 essential hypertensive patients determining: The Trp64Arg mutation of the beta-3-adrenergic receptor by PCR, lipoprotein profile by standard laboratory methods, membrane lipid composition by IATROSCAN and erythrocyte sodium lithium countertransport by Canessa technique. Patients with the mutation as compared with those without it showed lower membrane cholesterol, membrane cholesterol phospholipids ratio and erythrocyte sodium lithium countertransport, however blood pressure and the other studied variables were similar in both groups of patients. After adjusting by sex sodium lithium countertransport activity remained significant. These data suggest that although the Trp64Arg mutation of the beta-3-adrenergic receptor is related with a different membrane lipid composition and erythrocyte sodium lithium countertransport values it does not contribute to blood pressure levels in essential hypertensive patients.

Cortisol, aldosterona diferentes formas de hipertensión: papel de al 1 p-hidroxiesteroide dehidrogenasa

El cortisol y la aldosterona tienen la misma afinidad por el receptor minera locorticoide del túbulo distal. Pese a que el cortisol circula en plasma a concentraciones más de 100 veces superiores a las de la aldosterona, en situaciones normales éste no ejerce acción mineralocorticoide. Ello es así gracias a la existencia de una enzima: la 11 beta-hidroxiesteroide dehidrogenasa, que degrada al cortisol a su metabolito biológicamente inactivo: la cortisona. Existen situaciones en las que la actividad de la enzima es deficiente y en ellas el cortisol ejerce una potente acción mineralocorticoide. El paradigma sería el síndrome de exceso aparente de mineralocorticoide o la ingesta masiva de regaliz. Sin embargo, existen otras situaciones en las que la actividad de la enzima podría ser deficitaria; entre ellas están el síndrome de Cushing, algunos modelos de hipertensión animal o incluso algunos pacientes con hipertensión esencial. De todo ello nos ocuparemos en las siguientes líneas (AU)

[The effect of the angiotensinogen M235T and the angiotensin-converting enzyme I/D polymorphisms on arterial hypertension and other cardiovascular risk factors]. / Influencia de los polimorfismos M235T del angiotensinógeno e I/D de la enzima conversiva de la angiotensina sobre la hipertensión arterial y otros factores de riesgo cardiovascular.

BACKGROUND: It has been reported the association between M235T angiotensinogen (AGT) and I/D angiotensin converting enzyme (ACE) gene polymorphisms and hypertension and other cardiovascular risk factors. However there are few data about Spanish population. So that we have studied the relationship among the aforementioned polymorphisms and hypertension and the possibility of association between any polymorphism and a worse cardiovascular risk profile. PATIENTS AND METHODS: 251 hypertensive and 245 control normotensive subjects were studied. The M235T AGT and the I/D ACE gene polymorphisms were determined by polymerase chain reaction (PCR). Family and personal history of cardiovascular disease, lipoprotein profile, microalbuminuria and left ventricular hypertrophy (LVH) by Sokolow index were analyzed in hypertensive patients. RESULTS: The distribution of the different polymorphisms was similar among hypertensive and normotensive subjects. There was not any relationship among AGT nor ACE genotypes and target organ damage. The II ACE genotype was associated with higher lipoprotein (a) (Lp[a]) levels and greater cerebrovascular disease family history and the MT AGT genotype with lower total cholesterol (TC) and triglycerides (TG) levels. CONCLUSIONS: In our study there was not any relationship between arterial hypertension and M235T AGT or I/D ACE gene polymorphisms. None specific genotype was associated with worse cardiovascular risk profile. The II ACE genotype was a predictor of cerebrovascular disease risk through higher levels of Lp(a) and the MT AGT genotype was associated with a better lipid profile.

[Study of the gene of hemochromatosis in first degree relatives of patient with porphyria cutanea tarda]. / Estudio del gen de la hemocromatosis en familiares en primer grado de una paciente con porfiria cutánea tarda.

BACKGROUND: Porphyria cutanea tarda (PCT) is characterized by a deficiency of uroprophyrinogen decarboxylase (URO-D). The activity of this enzyme is decreased in the presence of iron-dependent disorders. A relationship between the hepatic hemosiderosis, which is present in most patients with PCT, and the status of the hemochromatosis gene has been observed. Particularly, two mutations of the gene have been described, one of them (Cys282Tyr) is related to the iron overload and might influence on the development of the clinical signs of PCT. PATIENTS AND METHODS: We have measured the transferrin saturation percentage and observed the status of the hemochromatosis gene in a patient diagnosed with PCT and in five of their relatives. RESULTS: The proband and one sister had a marked increase of uroporphyrins and iron overload, and both had the mutation Cys282Tyr, which was also present in the mother. CONCLUSIONS: This is the first study measuring iron overload and hemochromatosis gene mutations in relatives, and not in patients with PCT. We think that the study of this family justifies the systematic investigation of these parameters in all first degree relatives of patients with PCT, to identify subjects at risk, who can benefit from prophylactic measures and early therapy.

Modifications induced by -10 degrees Trendelenburg's posture in sodium tubular handling in patients with essential hypertension.

In essential hypertensive patients "exaggerated natriuresis" is a response to acute volume expansion. However, the underlying mechanisms for this remain to be determined. We studied 19 patients with essential hypertension (HP) and 9 normotensive subjects (NS). In all examined subjects the response to acute central volume expansion, without the plasma compositional change that Trendelenburg's position involves, was evaluated during 90 min (period T) after a similar period of deambulation (period D). Mean blood pressure (MBP), tubular sodium handling by the lithium clearance technique, plasma renin activity (PRA), plasma aldosterone (PA), plasma catecholamines and urine prostaglandine E2 and kallikrein were assessed after D and T. MBP was significantly higher in HP than in NS (p = 0.00001). HP showed "exaggerated natriuresis" after T (fractional excretion of sodium increased from 0.55 +/- 0.1% after D to 1.20 +/- 0.2% after T, p < 0.01). This was because of a decrease in their proximal fractional reabsorption of sodium (from 74.96 +/- 1.8% after D to 62.50 +/- 2.8% after T, p < 0.01). Plasma epinephrine and plasma dopamine after T were significantly lower than in standing position in HP (p < 0.01) but no in NS. The decrease in plasma renin activity after T in HP was 53%, and 32% in NS. There were not any significant differences between groups in the other neurohormonal systems studied. We conclude that the major determinant of "exaggerated natriuresis" in hypertensive patients is a higher stimulation of the cardiopulmonary receptors following Trendelenburg's position and consequently stronger reflex inhibition of sympathetic system activity and renin-angiotensin II activity. The "exaggerated natriuresis" after Trendelenburg's position in HP was an expression of abnormal pressure natriuresis.

[Transmembrane Na+ transport kinetics in arterial hypertension: relations with vascular risk parameters]. / Cinética del transporte transmembranoso de Na+ en la hipertensión arterial: relación con los parámetros de riesgo vascular.

BACKGROUND: To characterize the possible existence of kinetic anomalies of four erythrocyte membrane sodium transport systems in a group of essential hypertensive patients, and to study the clinical and biochemical profile of those with anomalies. METHODS: We studied 33 essential hypertensive patients and 33 normotensive controls. The kinetics (maximal rate and apparent dissociation constant for internal sodium) of Na(+)-K+ pump, Na(+)-K(+)-Cl- cotransport and Na(+)-Li+ countertransport was calculated after a sodium loading procedure, according to the methods of Garay; the passive Na+ permeability was also determined. RESULTS: The studied kinetic parameters were not significantly different in both groups. Nevertheless, we found a group of hypertensive patients with some transport abnormalities: increased intracellular sodium (9.1%), accelerated Na+ passive permeability (9.1%), lower activity of the Na(+)-K+ pump (7.1%) and the Na(+)-K(+)-Cl- cotransport (4%) and an increased maximal rate of the Na(+)-Li+ countertransport (11.8%). Na+Li+ countertransport activity was statistically related to plasma levels of urea, creatinine, glucose and LDL-cholesterol, and the activity of the Na(+)-K(+)-Cl- cotransport was related to plasma uric acid. The hypertensive patients with sodium transport anomalies showed higher body mass index, uric acid plasma levels and atherogenic index than those without these kind of anomalies, and they also showed lowered HDL-cholesterol plasma levels. CONCLUSIONS: A small group of essential hypertensive patients (around 31%) show kinetic alterations of sodium transport systems. There is a relation between Na(+)-Li+ countertransport activity and some cardiovascular risk parameters. Hypertensive patients with transport anomalies are a group with an increased cardiovascular risk.

[Influence of arterial pressure and plasma renin activity on tubular reabsorption of sodium]. / Influencia de la presión arterial y de la actividad de renina plasmática sobre la reabsorción tubular de sodio.

BACKGROUND: With the aim of confirming the possible existence of an increase in the fractional proximal reabsorption of sodium in the development of essential hypertension, the tubular dynamics of sodium were compared by the lithium clearance technique in a group of hypertensive patients and controls. METHODS: Following a week of drug suspension 186 patients with slight or moderate essential hypertension and 37 normal subjects with homogeneous sodium ingestion were studied. A clearing period of 90 minutes prior to the administration of a tracing doses of lithium was considered to calculate the fractional proximal and distal reabsorption of sodium in terms of glomerular filtration. In addition to global comparison of the measurements, the hypertensives were classified and compared according to mean arterial pressure (MAP) and percentages of plasma renin activity (PRA). RESULTS: No differences were found in tubular dynamics of sodium between hypertensive and normotensive patients. Neither did the degree of hypertension induce differences. However, upon classifying the patients according to PRA, it was found that those with PRA higher than 0.5 ng/ml-1/h-1 had less secondary natriuresis to a greater fractional distal reabsorption of sodium (p < 0.05). CONCLUSIONS: The findings of the this study do not support the possible existence of a primary defect of the transport of sodium in the proximal tubule in the origin and/or maintenance of essential arterial hypertension.

[Renovascular hypertension and Takayasu disease]. / Hipertensión vasculorrenal y enfermedad de Takayasu.

We present three cases of Takayasu disease which were peculiar because all three of them first manifested as vasculorenal hypertension. The pathogenic mechanisms of hypertension in this disease are reviewed, being renal arteries stenosis the most important mechanism. The great prognostic and therapeutic implications of hypertension in these patients made us suggest the performance of arteriographies of supraaortic trunks in all cases of vasculorenal arterial hypertension associated to certain clinical, analytical and/or arteriographic criteria which are mentioned.

[The influence of changes in the blood pressure and plasma renin activity on the natriuretic effect of nifedipine]. / Influencia de las modificaciones tensionales y de la actividad de renina plasmática sobre el efecto natriurético de nifedipino.

BACKGROUND: The possible influence of the variations in blood pressure and the plasma renin activity (PRA) after the administration of nifedipine (NIF) on the natriuretic effect of this calcium antagonist were evaluated. METHODS: The differences in the values of sodium excretion and tubular reabsorption were evaluated in 18 patients with essential hypertension with the method of the lithium clearance before and after the administration of a sublingual NIF dose. RESULTS: An increase in sodium excretion at the expense of a smaller distal reabsorption was found after NIF administration, without differences in patients with (n = 9) or without (n = 9) increase in PRA after NIF administration. The differences in several parameters when patients were classified depending on whether their mean blood pressure was reduced (n = 8) in more than 10% or not (n = 10) 90 minutes after NIF administration are discussed. CONCLUSIONS: Natriuresis induced by nifedipine is due to a diminished distal reabsorption of sodium. This effect is independent of PRA or its changes. On the other hand, the differences found in subgroups with different blood pressure response support the hypothesis that there are two populations of patients with essential hypertension depending on their acute response to calcium antagonists.

[Differences in the renal handling of sodium according to the response to captopril]. / Diferencias en el manejo renal de sodio según la respuesta al captopril.

We study the modifications of sodium tubular resorption, measured by lithium clearance after a single dosage of sublingual captopril, administered to 24 patients afflicted with nonfiltration after captopril produced an increase of proximal resorption of sodium, compensated by minor distal resorption, keeping a constant natriuresis. The different effects of captopril on blood pressure create 2 groups: a) patients who showed a decrease of blood pressure (n = 14), where a fall of distal resorption of sodium simultaneous with an increase of fractional sodium excretion was registered, and b) patients who did not experience changes in blood pressure nor changes after tubular function tests.