ABSTRACT
Recent studies have shown that cardiovascular events and end-organ damage occur more frequently in patients with salt-sensitive essential hypertension (SH) than in salt-resistant essential hypertension (RH). Nitric oxide (NO) plays an important role in regulating the pressure-natriuresis relationship. Therefore impaired NO synthesis may produce or aggravate salt-sensitive hypertension. This study was conducted to determine the hormonal levels and nitric oxide metabolites in hypertensive patients. 25 patients underwent salt sensitivity testing. 24 h ambulatory blood pressure was recorded after a 5-day period on low salt diet (20 mEq/d) and after a 5-day period on a high salt diet (200 mEq/d). Subjects showing > or = 10 mmHg increase in mean BP when changing from low to high dietary salt intake were classified as salt sensitive and as salt resistant when the BP changes were < 10 mmHg. Based on BP recordings 13 patients were characterised as white coat hypertension (WC), 13 patients as salt resistant (SR) and 12 as salt sensitive (SS). A significative relationship was seen between plasma glucose-insulin concentration and body mass index. The ventricular mass index was similar in SS and SR patients. The plasma uric acid, triglicerides and PAI-I were elevated in SS compared with SR, and control group (C). During low sodium intake, plasma renin and aldosterone were decreased in SS compared with SR, and C. No differences in plasma catecholamines or their changes with intake sodium modifications were seen among the patients. During high sodium intake urinary NO excretion increased in SR (38 +/- 9 vs 18 +/- 2 mg/g creat), and C (24 +/- 2 vs 16 +/- 3 mg/g creat) (p < 0.01) but not in SS patients (21 +/- 3 vs 26 +/- 4 mg/g creat). The NO excretion changes showed negative correlation with BP changes (r = 0.49, p < 0.01). During low sodium intake, SR and SS patients showed a normal nocturnal decrease of BP (dippers). During high sodium intake SS patients became non-dippers. Our results showed that patients with salt sensitive hypertension displayed a suppressed renin-aldosterone system, an attenuated nocturnal decline in blood pressure on high-salt diet and an impairment of endothelial function. The relationship between urinary nitrate excretion and arterial pressure suggest that the salt sensitivity of arterial pressure may be related bo blunted generation of endogenous nitric oxide.
Subject(s)
Aldosterone/analysis , Diet, Sodium-Restricted , Endothelium, Vascular/physiology , Hypertension/physiopathology , Nitric Oxide/physiology , Renin/blood , Adult , Blood Glucose/analysis , Blood Pressure , Circadian Rhythm , Data Interpretation, Statistical , Female , Hemodynamics , Humans , Hypertension/blood , Hypertension/urine , Insulin/blood , Logistic Models , Male , Middle Aged , Nitric Oxide/biosynthesis , Nitric Oxide/urine , Time FactorsABSTRACT
Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines, bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane interaction can induce production of these mediators. HD can also induce changes of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of this study was to investigate the effect of HD, using cuprophane (C, polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha), bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was similar with the three membranes. Cuprophane HD induced a significant increase in i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No changes were found in PAN and SPAN HD. The TNF-alpha values increased significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes of bradykinin concentration were found during HD. A significant decrease of ADA and nitrate levels was observed during HD with three membranes. No significant correlation was found between percentage increase in i-NOS activity and the changes in other parameters. These findings suggest that HD with bioincompatible membranes can induce activation of cellular i-NOS.
Subject(s)
Arginine/metabolism , Nitric Oxide/metabolism , Renal Dialysis , Adult , Arginine/analogs & derivatives , Female , Humans , Male , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
El óxido nítrico (ON) deriva de la acción de la óxido nítrico sintasa (ONS). Una de las isoformas de esta enzima, la ONS tipo II puede ser inducida (ONS-i) por diversos estímulos como citoquinas, endotoxinas y bradiquinina entre otros. Durante la Hemodiálisis (HD) pueden generarse, dependiendo de las características de la membrana, estos mediadores. La HD puede también inducir cambios en la concentración de sustancias con capacidad de inhibir la ONS como dimetil-L-arginina asimétrica (DAA).En el presente trabajo se analizan los efectos de la HD con membranas de diferente biocompatibilidad cuprofán (C), poliacrilonitrilo (PAN) y poliacrilonitrilo especial (SPAN) en la actividad celular de la ONS-i, en los niveles de activadores de la ONS como factor de necrosis tumoral (TNF-a) y bradiquinina, y de inhibidores de la ONS como la DAA, y los cambios de nitratos, marcadores de la generación de ON. La actividad de la ONS-i celular pre-HD fue similar en todas las membranas. Tras la HD se evidenció un aumento significativo de la actividad ONS-i en la membrana de C (31 ñ 10 frente a 48 ñ 23 fmol -1.106 células, p < 0,05) mientras que no se modificó en las membranas de PAN y SPAN (31 ñ 9 frente a 31 ñ 6 y 44 ñ 14 frente a 34 ñ 11 fmol-1.106 células, respectivamente). En la HD con C se observó un aumento significativo de TNFa. Esta monoquina descendió tras la HD con PAN y no se modificó en la HD con SPAN. Con ninguna de las membranas se observaron modificaciones significativas de la bradiquinina. Con los tres procedimientos se observó un descenso significativo de los niveles de DAA y nitratos en el transcurso de la HD. No se observó correlación significativa entre las modificaciones de la actividad de la ONS-i celular y las variaciones de TNFalfa, bradiquinina, DAA, nitratos ni los valores de la presión arterial. Estos resultados evidencian que durante l a HD puede producirse un aumento de la actividad de la ONS-i celular por mecanismos relacionados con la biocompatibilidad de la membrana de diálisis. Por otra parte, la determinación de nitratos no es útil como marcador de la generación de ON durante la HD debido a sus pérdidas transdialíticas (AU)