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E Nava

Publications and source records attributed to E Nava.

At least 37 records · Page 2Linked to original sources
PubMed1996

Nitric oxide synthase activity in renal cortex and medulla of normotensive and spontaneously hypertensive rats.

The medullary portion of the kidney plays a crucial role in the control of sodium and water excretion and arterial pressure. This control is anomalous in hypertension and may be related to an impaired renal nitric oxide (NO) production. We have measured the activity of NO synthase (NOS) in the renal medulla, renal cortex, heart, and aorta from normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Enzyme activity was determined by measuring the conversion of 14C-L-arginine to 14C-L-citrulline. Ca2+-dependent NOS activity was considerably higher in the renal medulla than in the other tissues studied, both in WKY and SHR. The medulla and heart of the SHR displayed a higher Ca2+-dependent NOS activity compared to that of WKY. No differences were found in the Ca2+-independent NOS activity, except for the renal cortex of the SHR, which was higher than in the rest of the tissues. These observations indicate that the renal medulla has a high relative capacity to synthesize NO and suggest that the impaired renal medullary control of arterial pressure of genetic hypertension is not due to a reduced NO production by the kidney.

Animals↗
PubMed1996

Cyclic guanosine 3',5' monophosphate concentrations in pre-eclampsia: effects of hydralazine.

OBJECTIVE: To elucidate the role of the L-arginine:nitric oxide pathway in pregnancy and pre-eclampsia. PARTICIPANTS: Pregnant women (nulliparous, age <25 years). Normotensive pregnancy (n=22) was defined when blood pressure remained at levels of <120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (n=22) had blood pressure measurements of >140/90 mmHg and proteinuria of >300 mg/l. Nonpregnant normotensive women (n=22) were studied as controls. STUDY DESIGN: Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5' monophosphate (GMP),arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine. RESULTS: L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD 15.7) microM] were increased significantly (P<0.05) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) microM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) microM]. Concentrations of cyclic GMP in plasma and urine increased significantly (P<0.05) in women treated with hydralazine. CONCLUSIONS: The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.

Adult↗
PubMed1996

Changes in nitric oxide release in vivo in response to vasoactive substances.

1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure.

Animals↗
PubMed1996

Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril.

The objective of this study was to examine the effects of long-term antihypertensive therapy on blood pressure and vascular responses of resistance arteries during prolonged inhibition of nitric oxide synthesis. Four groups of 6-week-old Wistar-Kyoto rats were treated with either placebo as controls or N omega-nitro-L-arginine methyl ester (L-NAME) alone or in combination with verapamil or with trandolapril. Drugs were given orally for 6 weeks or short-term in vitro to vessels obtained from untreated rats. Endothelium-dependent and -independent relaxations as well as contractions were studied in isolated perfused mesenteric and renal arteries with an arteriograph. Kidney nitric oxide synthase activity was also evaluated. Verapamil and trandolapril prevented the increase in systolic blood pressure and the blunted acetylcholine-induced relaxations that occurred with L-NAME treatment without improving the nitric oxide synthase activity. Both antihypertensive regimens also normalized sensitivity to sodium nitroprusside, which was enhanced by L-NAME. In contrast, short-term in vitro preincubation with verapamil or trandolaprilat in the presence of L-NAME did not improve the impaired relaxations to acetylcholine. Long-term but not short-term therapy with a calcium antagonist or angiotensin-converting enzyme inhibitor improved the blunted endothelium-dependent relaxations in nitric oxide-deficient hypertension. These findings strongly suggest that the role of other vasodilator systems, which normally do not regulate vascular tone, is enhanced with long-term but not short-term treatment with these drugs. These observations emphasize the potential importance of these treatments in the management of hypertension in which nitric oxide production is diminished.

Animals↗
PubMed1995

Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension.

BACKGROUND: We analyzed the activity of nitric oxide synthase in the rat heart to study whether this activity is affected by high blood pressure. Hearts from young (3 to 4 weeks old) and adult (15 to 25 weeks old) Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were excised and frozen in liquid nitrogen. The activities of Ca(2+)-dependent (cNOS) and Ca(2+)-independent (iNOS) were determined in homogenized tissues by measuring the conversion of [14C]-L-arginine to [14C]-L-citrulline in the presence or absence of either EGTA (1 mmol/L) or EGTA plus NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L each). METHODS AND RESULTS: Arterial pressure was higher in adult SHR than in young SHR and WKY rats of both ages (P < .01). The cNOS activity was two to three times higher in hypertensive than in normotensive hearts (P = .01 to P = .04). No significant activity of iNOS was detected in any tissue. Studies of the right and left ventricles demonstrated a higher cNOS activity in the left sides of the hearts of adult SHR (P < .05). No differences were found in hearts from WKY rats. Selective removal of endocardial or coronary endothelial cells in hearts of SHR and WKY rats substantially reduced cNOS activity (P < .01). CONCLUSIONS: The cNOS activity is upregulated in cardiac endothelial cells of genetically hypertensive rats. The high activity of cardiac cNOS is related to increased arterial pressure of these animals. We propose that in the heart, endothelial cells respond with a higher production of nitric oxide as a compensatory mechanism against high blood pressure and its damaging effects in this organ.

Amino Acid Oxidoreductases↗
PubMed1995

Endothelium-derived vasoactive factors in hypertension: nitric oxide and endothelin.

ENDOTHELIUM-DERIVED NITRIC OXIDE: The endothelium is a source of vasoactive factors among which the most relevant are nitric oxide and endothelin. Nitric oxide is synthesized from L-arginine by a family of nitric oxide synthases and is a widespread biological mediator. It is implicated in many physiological and pathophysiological processes, including a variety of cardiovascular diseases like hypertension. NITRIC OXIDE AND HYPERTENSION: The release of nitric oxide seems to be modulated by changes in blood pressure. However, the role of nitric oxide in hypertension is still controversial and seems to vary depending on the stage of the disease and the model studied. In spontaneous hypertension, the production of nitric oxide is increased but inefficacious, probably because of increased inactivation or scavenging. In the heart the production of nitric oxide seems to be increased, probably as a compensatory mechanism against hypertension. In salt-induced hypertension, nitric oxide production may be impaired. In human hypertension, pharmacological experiments reveal an impaired nitric oxide dilator mechanism. In pulmonary hypertension, the use of nitric oxide gas inhalation has been proposed as a future therapy for this condition. ENDOTHELIN: Endothelin-1 is a potent vasoconstrictor peptide produced and released from endothelial cells. In isolated blood vessels, endothelin causes profound contraction. The hemodynamic effects of endothelin can be explained by the activation of two endothelin receptors, ETA and ETB. The relationship between endothelin and hypertension is not clear. Although plasma endothelin levels are normal in most patients with essential hypertension, the hypertensive blood vessel wall may contract more profoundly in response to the peptide; hence, endothelin antagonists may have antihypertensive effects in patients with hypertension.

Animals↗
PubMed1995

Expression of nitric oxide synthase isoforms in the thyroid gland: evidence for a role of nitric oxide in vascular control during goiter formation.

The thyroid gland is a highly vascular tissue, and its blood flow changes dramatically in various pathological conditions. Although the mechanisms regulating these changes in vascularity and blood flow are not well understood, candidate mediators include endothelin-1 (ET-1) and nitric oxide (NO). In the present study, we used a reverse transcriptase-polymerase chain reaction assay to determine which components of these vasoregulatory pathways are present in the thyroid and to analyze changes in gene expression in an experimental model of goiter formation and involution. Expression of messenger RNAs (mRNAs) encoding ET-1, ET receptors (ETA and ETB), ET-converting enzyme, and the three nitric oxide synthase (NOS) isoforms (NOS I, NOS II, and NOS III) was readily detected in the rat thyroid. After goiter formation was induced by thiouracil and a low iodine diet, there was increased expression of the genes encoding ET-related proteins (ET-1, 3.2-fold; ETA, 2.9-fold; ETB, 3.5-fold) as well as two of the three NOS isoforms (NOS I, 2.7-fold; NOS III, 4.9-fold). During iodide-induced involution, the ET-related mRNA levels remained elevated, whereas those of the two NOS isoforms returned to basal values. ET-converting enzyme, NOS II, and thyroglobulin mRNAs were minimally affected in this model, providing evidence for selective regulation of these genes. To assess whether NO plays a role in vascular changes during goiter formation, animals were treated with a NOS inhibitor, N-nitro-L-arginine methyl ester (NAME). NOS activity in the thyroid was inhibited by more than 75% after treatment with NAME. Thyroid hormone and TSH levels were unchanged. Although NAME had little effect on overall thyroid size, vascular expansion during goiter formation was decreased by 36%. We conclude that the thyroid gland expresses a complex network of vasoactive genes whose expression is regulated dynamically during thyroid goiter formation and involution. NO production and probably other locally produced vasoactive substances are involved in changes in thyroid vascularization.

Animals↗
PubMed1995

Nitric oxide in cardiovascular diseases.

Nitric oxide (NO), synthesized from L-arginine by a family of NO synthases (NOS), is a widespread biological mediator implicated in many physiological and pathophysiological processes, including a variety of cardiovascular diseases. Endothelium-derived NO, synthesized by a constitutive NOS, is involved in hypertension, atherosclerosis and certain heart diseases. In hypertension and atherosclerosis the role of NO is still controversial and seems to vary depending on the stage of the disease and model studied. In spontaneous hypertension, the production of NO is increased, but inefficacious, probably because of increased inactivation. In salt-induced hypertension NO production may be impaired. In atherosclerosis, an enhanced degradation of NO by superoxide radicals may explain the reduced endothelium-dependent relaxations. In pulmonary hypertension, the use of NO gas inhalation has been proposed as a future therapy for this condition. In the heart, NO regulates coronary flow and myocardial function; both functions are altered in coronary artery disease and cardiomyopathy. Nitric oxide synthesized by the inducible NOS takes part in several immunopathological diseases, such as endotoxin shock, which can particularly affect the heart. In endotoxaemia inducible NOS is overexpressed and the excess in NO production may account for the impaired cardiac performance of this condition. The overproduction of NO occurring in endotoxin shock is also responsible for the hypotension, catecholamine resistance and tissue damage characteristic of this disease. Treatment with inhibitors of NO synthesis is a promise for the future.

Arteriosclerosis↗
PubMed1992

Receptor-mediated effect of a synthetic thromboxane-analogue on cytosolic calcium in isolated proximal tubules.

The aims of this study were to measure cytosolic calcium concentration -[Ca2+]i- under resting conditions in isolated renal proximal tubules and to analyze the effect of U-46619 (stable analogue of thromboxane A2/PGH2 on [Ca2+]i in a mammalian epithelium. Proximal tubules were dissected out from male New Zealand rabbits (2.5 to 3.0 kg). After isolation they were washed twice and resuspended in 2 ml phosphate buffer solution (PBS). Tubules were loaded with Quin 2-AM (25 microM) for 15 min. After washing with PBS to eliminate the excess of extracellular Quin 2, fluorescence was measured at 340 nm excitation and 490 emission, under resting conditions and after stimulation. U 46619 (from 10 nm to 10 mM) increased [Ca2+]i in a concentration-dependent pattern. Exposure to an antagonist of the thromboxane receptor (S-145) blocked the response to U-46619. Removal of external calcium abolished the response to U-46619. Change of PBS for Ringer-choline blunted the response to thromboxane analogue. Our results indicate that U-46619 increases cytosolic calcium through a receptor-mediated mechanism that requires external calcium to operate. Blockade of the response in the absence of external sodium suggests that Na+/Ca2+ exchanger participates in this response.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

The role of nitric oxide in endotoxic shock: effects of NG-monomethyl-L-arginine.

The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG-monomethyl-L-arginine (L-NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of L-NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of L-NMMA were given a continuous infusion of S-nitroso-N-acetylpenicillamine (SNAP, 300 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1992

Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium.

1. We have investigated whether the myocardium and isolated cardiac myocytes can express a Ca(2+)-independent NO synthase after treatment with endotoxin or cytokines. Nitric oxide synthesis was measured in cytosols from the left ventricular wall from rats treated with endotoxin, or from freshly isolated myocytes from adult rats treated in vitro with cytokines. 2. Cytosols from the ventricle of saline-treated control animals showed only Ca(2+)-dependent NO synthesis. After treatment with endotoxin, the expression of an inducible, Ca(2+)-independent NO synthase was observed. The activity of this enzyme was maximal at 6 h and returned towards control levels by 18 h; no alterations occurred in the Ca(2+)-dependent NO synthase activity. Parallel to this enzyme induction there was an increase in myocardial guanosine 3':5'-cyclic monophosphate (cyclic GMP) and plasma nitrite and nitrate (NOx-). All these changes were prevented by pretreatment of the rats with dexamethasone. 3. Myocytes possessed Ca(2+)-dependent NO synthase activity and expressed, after treatment with tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), a Ca(2+)-independent NO synthase, the induction of which was prevented by dexamethasone and cycloheximide. 4. Since increases in cyclic GMP levels in the heart are associated with reduced myocardial contractility, it is possible that the enhanced production of NO by a Ca(2+)-independent enzyme accounts, at least in part, for the depression of myocardial contractility seen in septic shock, cardiomyopathies, allograft rejection, burn trauma, as well as during anti-tumour therapy with cytokines.

Amino Acid Oxidoreductases↗
PubMed1990

Trypanosoma cruzi infection in the Mexican state of Guerrero: a seroepidemiological (ELISA) survey of 20 communities.

The enzyme linked immunosorbent assay (ELISA) was used to analyse 4372 blood samples from residents of 978 households in 20 representative communities in the Mexican state of Guerrero. Seventy-five individuals had very high titres of antibodies against Trypanosoma cruzi. Samples with intermediate optical density values, despite overlapping values with several control positives on a single-well test, did not sustain their positivity at high dilutions. 'Intermediate positives' had a different distribution among the 20 communities to samples sustaining reactivity at high dilutions, indicating possible cross-reactivity with another infectious agent. The finding of seropositive children under the age of 10 years in the Costa Chica, Acapulco and the Tierra Caliente regions, with family clustering of putative cases, indicates that recent transmission must be considered. Very few people interviewed in the 20 communities knew the triatomine bug could transmit a disease.

Age Factors↗
PubMed1985

Flow cytometric analysis of DNA content in human bladder tumors and irrigation fluids.

Flow cytometry (FCM) was used to study the DNA distribution of 99 tumor biopsy specimens and 41 bladder irrigation samples from patients with transitional cell carcinoma of the bladder. For tumor biopsy and cystectomy specimens, the frequency of aneuploidy increased with advancing tumor stage and grade. All T0 tumors were diploid. Twenty-seven percent of T1, 71.4% of T2, and 75% of T3 and T4 tumors were aneuploid. All Grade I tumors were diploid. Thirty percent of Grade II and 76.9% of Grade III tumors were aneuploid. The frequency of aneuploidy of tumors in the early stages (Ta, T1) is similar to the incidence of subsequent progression by these tumors described in the literature. For irrigation fluids, the relationship between grade and stage and the frequency of aneuploidy was similar to the relationship seen with tumor specimens. All four patients with only carcinoma in situ had aneuploid cells in their irrigations. The comparison of FCM data of bladder biopsy and bladder irrigation from the same cystoscopic evaluation suggests adequate representation of tumor cells in the irrigation fluids for almost all cases. The authors conclude that DNA ploidy analysis by FCM appears useful in a clinically important group of patients with aneuploid superficial tumors of moderate or high grade. Bladder irrigation analysis appears useful in the follow-up of patients with a history of carcinoma in situ and those with aneuploid tumors.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Simplification of the polymerase chain reaction for detection of Mycobacterium tuberculosis in the tropics.

It has been suggested that the technical complexities, the expense of equipment and consumables, and problems associated with contamination make the polymerase chain reaction (PCR) inappropriate for use in developing countries. These problems were addressed using a novel one-tube nested PCR, small reaction volumes and a 'three room' system for the detection of Mycobacterium tuberculosis. The PCR of sputum samples dried on small filter paper disks was also investigated. Using this strategy 5 smear-positive and 15 smear-negative specimens were correctly identified by PCR. This method of sample collection has the advantage that samples can be sent by post and stored in a minimum of space, and remain viable for PCR for at least 4 years after collection. These and future modifications to the PCR protocol will make the assay more suitable for use in the tropics.

Base Sequence↗
PubMedDate not supplied

Inhibition of nitric oxide synthesis in septic shock: how much is beneficial?

Hypotension in septic shock is often resistant to treatment with vasoconstrictors and appears to be mediated by production of nitric oxide (NO). Reversal of endotoxin-induced hypotension in rats was achieved by intravenous injection of 30 mg/kg NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endogenous NO synthesis. A lower dose of 3 mg/kg L-NMMA was ineffective, but 300 mg/kg L-NMMA accelerated and enhanced the fall in blood pressure. NO synthase inhibitors may be helpful in the treatment of hypotension associated with sepsis or therapeutic use of cytokines, but complete inhibition of endogenous NO synthesis may be counterproductive.

Animals↗
PubMedDate not supplied

Discrimination of various contributions to the absorbed dose in BNCT: Fricke-gel imaging and intercomparison with other experimental results.

A method is described for the 3D measurements of absorbed dose in a ferrous sulphate gel phantom, exposed in the thermal column of a nuclear reactor. The method, studied for Boron Neutron Capture Therapy (BNCT) purposes, allows absorbed dose imaging and profiling, with the separation of different contributions coming from different secondary radiations, generated from thermal neutrons. In fact, the biological effectiveness of the different radiations is different. Tests with conventional dosimeters were performed too.

Boron Neutron Capture Therapy↗