Biomedical subjects

M Ferrer

Publications and source records attributed to M Ferrer.

At least 73 records · Page 4Linked to original sources

PubMed1999

Accumulation of heavy metals and As in wetland birds in the area around Doñana National Park affected by the Aznalcollar toxic spill.

The impact of the spill from the mine in Aznalcollar (Seville, Spain) on waterfowl in the Doñana National Park is assessed. The concentrations of Cu, Pb, Cd, Zn nd As in the liver and eggs of 16 species of waterfowl found dead in the Park between April and November 1998 were determined. The highest levels were found for Zn, followed by Cu, Pb, Cd and As. The main parameters related to the accumulation of these elements in the waterfowl studied were species and trophic level. The other variables studied--distance from the spill, days of exposure, sex, size, and age--are important, although this depends on the element studied. Zn and Cu from the spill have entered the food chain of the aquatic birds studied, but Cd, Pb and As have not. There is currently no evidence to suggest that the trace element concentrations measured have reached toxic levels.

Accidents, Occupational↗

PubMed1999

Trace elements in blood collected from birds feeding in the area around Doñana National Park affected by the toxic spill from the Aznacóllar mine.

A long-term monitoring plan was established to study if bird populations around Doñana National Park were affected by the toxic spill from the Aznalcóllar mine. The concentrations of Zn, Pb, As, Cu, Sb, Co, Tl and Cd in the blood of 11 bird species feeding in the area were determined. The parameters which most affect the accumulation of trace elements in the birds studied are, firstly, species and secondly, trophic position, sex, days of exposure and weight. In some individuals, Zn and Cu occurred at higher levels than the reference values for contaminated areas. Concentrations of Pb and Cd in a considerable number of individuals were higher than those found in birds from uncontaminated areas. The present data, together with the lack of data on blood metal concentration prior to the spill, do not offer any conclusive evidence of the influence of the spill on avian blood metal concentrations.

Accidents, Occupational↗

PubMed1999

Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial.

BACKGROUND: Risk factors for nosocomial pneumonia, such as gastro-oesophageal reflux and subsequent aspiration, can be reduced by semirecumbent body position in intensive-care patients. The objective of this study was to assess whether the incidence of nosocomial pneumonia can also be reduced by this measure. METHODS: This trial was stopped after the planned interim analysis. 86 intubated and mechanically ventilated patients of one medical and one respiratory intensive-care unit at a tertiary-care university hospital were randomly assigned to semirecumbent (n=39) or supine (n=47) body position. The frequency of clinically suspected and microbiologically confirmed nosocomial pneumonia (clinical plus quantitative bacteriological criteria) was assessed in both groups. Body position was analysed together with known risk factors for nosocomial pneumonia. FINDINGS: The frequency of clinically suspected nosocomial pneumonia was lower in the semirecumbent group than in the supine group (three of 39 [8%] vs 16 of 47 [34%]; 95% CI for difference 10.0-42.0, p=0.003). This was also true for microbiologically confirmed pneumonia (semirecumbent 2/39 [5%] vs supine 11/47 [23%]; 4.2-31.8, p=0.018). Supine body position (odds ratio 6.8 [1.7-26.7], p=0.006) and enteral nutrition (5.7 [1.5-22.8], p=0.013) were independent risk factors for nosocomial pneumonia and the frequency was highest for patients receiving enteral nutrition in the supine body position (14/28, 50%). Mechanical ventilation for 7 days or more (10.9 [3.0-40.4], p=0.001) and a Glasgow coma scale score of less than 9 were additional risk factors. INTERPRETATION: The semirecumbent body position reduces frequency and risk of nosocomial pneumonia, especially in patients who receive enteral nutrition. The risk of nosocomial pneumonia is increased by long-duration mechanical ventilation and decreased consciousness.

Aged↗

PubMed1999

Lipase-catalyzed regioselective acylation of sucrose in two-solvent mixtures.

The enzymatic synthesis of 6-O-lauroylsucrose and 6-O-palmitoylsucrose was performed by transesterification of sucrose with the corresponding vinyl esters in a medium constituted by two solvents. More specifically, the acylation was carried out in 2-methyl-2-butanol (tert-amyl alcohol) containing a low percentage (not higher than 20%) of dimethyl sulfoxide. Several lipases were able to catalyze the transesterification, but that from Humicola lanuginosa (adsorbed on diatomaceous earth) was particularly useful. We optimized the synthesis of 6-O-lauroylsucrose varying the percentage and nature of the cosolvent, the molar ratio sucrose/vinyl laurate, the nature of bulk solvent and the enzyme content. Under the best conditions (2-methyl-2-butanol/DMSO 4:1 v/v), a sucrose conversion of 70% to 6-O-lauroylsucrose was achieved in 24 h using 50 mg biocatalyst/mL. As a side process, a low percentage (<5% in 24 h) of the initial sucrose is converted into the diesters 6,1'-di-O-lauroylsucrose and 6,6'-di-O-lauroylsucrose. The above methodology was also extended to the synthesis of 6-O-palmitoylsucrose. The acylation process was even faster, giving rise to an 80% conversion to monoester in 48 h using 25 mg biocatalyst/mL. This study shows that the use of two-solvent mixtures may become a feasible alternative for the synthesis of sucrose esters, allowing to exploit the catalytic potential of lipases.

Acylation↗

PubMed1999

[Measurement of the perceived impact of sleep problems: the Spanish version of the functional outcomes sleep questionnaire and the Epworth sleepiness scale].

BACKGROUND: Excessive daytime sleepiness is a frequent symptom and a public health problem due to its association with automobile and work related accidents. The aim of this study was to develop and carry out a preliminary assessment of the Spanish version of the functional outcomes sleep questionnaire and the Epworth sleepiness scale, two instruments designed to evaluate patients with sleep disorders. MATERIAL AND METHODS: For the adaptation, the forward and back-translation method by bilinguals was used with professional and lay panel. Once tested for feasibility and comprehension, 39 patients with obstructive sleep apnea syndrome completed the Spanish version of the FOSQ and the Epworth sleepiness scale, together with a question on self-rated health status. RESULTS: Difficulty of translation was assessed as low and the naturalness of Spanish expressions as high for all the items of the questionnaires except for the response options of the Epworth sleepiness scale. Both questionnaires showed higher reliability than the standard proposed for individual comparisons (Cronbach's alpha > 0.9). The FOSQ vigilance scale showed a high correlation with the Epworth score (r = -0.79), while for the other scales of the FOSQ correlations were moderate (r ranging from -0.52 to -0.68). Patients who reported "regular" or "poor" health had significantly worse scores for most of the FOSQ scales. CONCLUSION: These results suggest that the Spanish versions of both questionnaires are conceptually equivalent to the originals and that they show similar characteristics of reliability and validity. The FOSQ vigilance scale assess daytime sleepiness similarly to Epworth but the others scales of the FOSQ provide additional information for these patients.

Female↗

PubMed1999

Effect of nasogastric tube size on gastroesophageal reflux and microaspiration in intubated patients.

BACKGROUND: Little evidence exists to support the theory that small-bore nasogastric tubes prevent gastroesophageal reflux and microaspiration in intubated patients. OBJECTIVE: To determine whether gastroesophageal reflux and microaspiration in intubated patients can be reduced by the use of a small-bore nasogastric tube. DESIGN: Randomized, two-period crossover trial. SETTING: Respiratory intensive care unit of a university hospital. PATIENTS: 17 patients intubated for more than 72 hours. INTERVENTIONS: Radioactive technetium colloid was instilled in each patient's stomach. Patients were studied with two nasogastric tubes (one tube with a 6.0-mm external bore and one tube with a 2.85-mm external bore) in randomized order; measurements of radioactive counts with the alternate size of nasogastric tube were repeated 72 hours after original measurements were taken. Sequential samples of serum, gastric juice, and pharyngeal and tracheal secretions were obtained. MEASUREMENTS: Comparison of the time course of radioactive counting in all samples (obtained during the use of each nasogastric tube size in each patient). RESULTS: The mean radioactive count of pharyngeal aspirates (P = 0.004) was greater than the baseline count at all time points, as was the cumulative radioactive count of pharyngeal aspirates 17 hours after the first dose of technetium colloid was administered (P = 0.001); however, the count of tracheal aspirates was never greater than the count at baseline. No differences were found between tube types when the time course and cumulative counts of pharyngeal and tracheal samples were compared. CONCLUSION: Small-bore nasogastric tubes in intubated patients do not reduce gastroesophageal reflux or microaspiration.

Cross-Over Studies↗

PubMed1999

Expression of a new isoform of the tumor susceptibility TSG101 protein lacking a leucine zipper domain in Burkitt lymphoma cell lines.

The tumor susceptibility gene, TSG101, has been identified as a candidate tumor suppressor gene. We have examined the expression of TSG101 in Burkitt lymphoma cell lines. Several aberrant messages were detected in all cell lines. Aberrant splice donor sites are located within exon 1 at positions 132, 154, 172 and 284. Splice acceptors are located at positions 847 and 1054 within exon 5. The aberrant messages are coexpressed with a normal message and could be the result of additional splicing reactions of the mature message that behaves as an intermediate. The normal message codes for 46 kDa protein (TSG101A). One aberrant message joins in frame nucleotides 283-1055 and codes for a protein isoform of 17 kDa (TSG101B), as demonstrated by in vitro translation assays. The TSG101B isoform lacks the leucine zipper near the C-terminus, a transcriptional repressor domain, and retains most of the N-terminal region which has homology to E2 ubiquitin regulatory enzymes and the CROC-1 transcriptional regulator. The TSG101B isoform was detected in sixteen out of twenty-two (72%) BL cell lines, but not in normal lymphoid populations. The presence of two TSG101 isoforms with different dimerization potential opens up a new level of regulation of the TSG101 proteins possibly affecting cell cycle regulation.

Amino Acid Sequence↗

PubMed1999

Comparison of performance-based and self-rated functional capacity in Spanish elderly.

Recent data have shown differences between Spain and the United States in the prevalence of reported disability among community elderly. Differences in reporting functional capacity by culture may contribute to these observed differences. The purpose of this study was to estimate the agreement between self-report of disability and performance-based measures for some basic mobility tasks in the community-dwelling elderly of a Mediterranean country. Interviews containing questions about difficulty for walking and rising from a chair, and performance-based measures (walking speed and chair stand tests) were carried out in 626 individuals aged 72 years and older in Barcelona, Spain. Kappa statistics were calculated, and logistic regression models were constructed to identify possible factors associated with under- and overreporting functional capacity. Moderate kappas (0.41-0.55) were found between self-report and performance-based measures. Patients who rated their health as "poor or very poor" were less likely to underreport disability (adjusted odds ratio (OR) = 0.2, 0.4) but more likely to overreport it (adjusted OR = 23.4, 9.9). No significant agreement differences by sex or informant source were found. These findings suggest that Spanish elderly self-report functional capacity accurately and that, contrary to previous results among US elderly, the direction of the observed disagreement is not systematic.

Activities of Daily Living↗

PubMed1999

Molecular genetic analysis of a compound heterozygote for the glycoprotein (GP) IIb gene associated with Glanzmann's thrombasthenia: disruption of the 674-687 disulfide bridge in GPIIb prevents surface exposure of GPIIb-IIIa complexes.

This work was aimed at elucidating the molecular genetic lesion(s) responsible for the thrombasthenic phenotype of a patient whose low platelet content of glycoprotein (GP) IIb-IIIa indicated that it was a case of type II Glanzmann's thrombasthenia (GT). The parents did not admit consanguinity and showed a reduced platelet content of GPIIb-IIIa. Polymerase chain reaction (PCR)-single-stranded conformational polymorphism analysis of genomic DNA showed no mutations in the patient's GPIIIa and two novel mutations in the GPIIb gene: one of them was a heterozygous splice junction mutation, a C-->A transversion, at position +2 of the exon 5-intron 5 boundary [IVS5(+2)C-->A] inherited from the father. The predicted effect of this mutation, insertion of intron 5 (76 bp) into the GPIIb-mRNA, was confirmed by reverse transcription-PCR analysis of platelet mRNA. The almost complete absence of this mutated form of GPIIb-mRNA suggests that it is very unstable. Virtually all of the proband's GPIIb-mRNA was accounted for by the allele inherited from the mother showing a T2113-->C transition that changes Cys674-->Arg674 disrupting the 674-687 intramolecular disulfide bridge. The proband showed a platelet accumulation of proGPIIb and minute amounts of GPIIb and GPIIIa. Moreover, transfection and immunoprecipitation analysis demonstrated that [Arg674]GPIIb is capable of forming a heterodimer complex with GPIIIa, but the rate of subunit maturation and the surface exposure of GPIIb-IIIa are strongly reduced. Thus, the intramolecular 674-687 disulfide bridge in GPIIb is essential for the normal processing of GPIIb-IIIa complexes. The additive effect of these two GPIIb mutations provides the molecular basis for the thrombasthenic phenotype of the proband.

Alleles↗

PubMed1999

Expression of aberrant functional and nonfunctional transcripts of the FHIT gene in Burkitt's lymphomas.

The 3p14.2 chromosome region, which contains the FHIT gene and the FRA3B fragile site, is frequently altered in carcinomas. We analyzed the expression of the FHIT gene in 21 Burkitt's lymphoma cell lines and normal lymphoid populations. Seventeen (80%) of these cell lines had a common aberrant FHIT transcript as well as the normal transcript. Exon 2 was often aberrantly spliced to several coding exons, skipping exons 3 and 4, which overlap FRA3B. Other aberrant transcripts lacked exons 4-7 or exons 5-8. Exon 5, which has the initiation codon, was the most commonly affected. In two cell lines, Raji and KK124, there were aberrant transcripts retaining only the coding exons, which were able to make a normal protein, as demonstrated by in vitro transcription-translation analysis. In these aberrant messages, the additional deletion of 11 nucleotides at the beginning of exon 10 resulted in loss of translation. The cell line Ramos did not have a normal transcript. Some transcripts had common insertions of unknown origin that replaced coding exons, mainly exons 6 and 7. None of these aberrant messages coded for a protein, whether normal or aberrant. Within an individual cell line, aberrant messages appeared to result from sequential splicing reactions of a transcriptional unit derived from one allele. There was no correlation between aberrant FHIT transcription and the type of Burkitt's lymphoma regarding chromosomal translocation or presence of Epstein-Barr virus. In normal tonsils, spleen, and peripheral blood lymphocytes, aberrant transcripts were not detected and might represent a very minor subpopulation if detectable.

Acid Anhydride Hydrolases↗

PubMed1999

Complement dependence of histamine release in chronic urticaria.

BACKGROUND: IgG autoantibodies directed to the alpha-subunit of the IgE receptor have been identified in 30% to 45% of patients with chronic urticaria. However, the exact mechanism by which histamine secretion is initiated is uncertain. OBJECTIVE: Histamine release from cutaneous mast cells may occur by cross-linking the IgE receptor or by activation of complement. Our goal is to distinguish these 2 possibilities. METHODS: We incubated human cutaneous mast cells with patient sera, decomplemented sera, or purified patient IgG. The IgG was also added to pooled normal serum or to sera deficient in either C2 or C5, and its ability to activate mast cells was assessed. Mast cells were incubated with human IgE myeloma to saturate alpha-subunits to determine the effect on histamine release. RESULTS: Patient sera released histamine (18.26% +/- 4.39%), but purified IgG from patients (5.5% +/- 4.3%) did not. Addition of the patient IgG to normal sera rendered the sera positive for histamine-releasing activity (18.4% +/- 4.3%), whereas control IgG or patient IgG added to C2- or C5-deficient sera did not release histamine. Histamine release with decomplemented patient sera was also diminished (8.34% +/- 4.3%). Preincubation of mast cells with a C5-blocking peptide decreased histamine release but was not statistically significant; there was a significant decrease after preincubating mast cells with IgE myeloma. CONCLUSION: The degranulation of mast cells by IgG autoantibodies in patients with chronic urticaria requires binding to the IgE receptor and activation of the classical complement cascade. Saturation of the IgE receptor with IgE inhibits such degranulation, presumably by preventing binding of the requisite IgG.

Cell Degranulation↗

PubMed1999

In vitro capacitation of dog spermatozoa as assessed by chlortetracycline staining.

We developed an assay for detecting capacitation and acrosome status in dog spermatozoa using chlortetracycline (CTC) as a fluorescent probe. Sperm cells were stained after incubation in modified canine capacitation medium (mCCM). Calcium ionophore A23187 permitted the induction of acrosomal exocytosis of capacitated sperm cells. Spermac staining and transmission electron microscopy were used as control tests to detect acrosome-reacted spermatozoa. Three different patterns of CTC distribution in the spermatozoa were found. These patterns were similar to those observed in other mammalian species. The CTC test was used to monitor the time course of the capacitation process in dogs. It was found that the kinetics of capacitation in canine sperm cells are similar to those observed in other mammals.

Acrosome Reaction↗

PubMed1999

Role of K+ channels and sodium pump in the vasodilation induced by acetylcholine, nitric oxide, and cyclic GMP in the rabbit aorta.

The endothelium-dependent relaxation caused by acetylcholine (ACh) in rabbit aorta segments was reduced by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester and by blockade of: Na+ pump with ouabain, large-conductance Ca2+-activated K+ (BK(Ca)) channels with charybdotoxin (ChTx), or voltage-dependent K+ (Kv) channels with 4-aminopyridine (4-AP). ACh relaxation was unaltered by glibenclamide, apamin, and Ba2+, blockers of ATP-sensitive K+ channels, small-conductance Ca2+-activated K+ channels, and inward rectifier K+ channels, respectively. The relaxation induced by exogenous NO and 8-bromocyclic GMP (8-BrcGMP) was similar in intact and endothelium-denuded segments, and it was reduced or unaltered by the same drugs used in the case of ACh. However, a 4-AP concentration 20-fold higher was necessary to reduce exogenous NO relaxation. These data suggest a resemblance in the mechanisms implicated in the relaxation elicited by ACh, exogenous NO, and 8-BrcGMP. Therefore, the relaxation caused by ACh is mainly mediated by endothelial NO, which in turn, enhances cGMP levels; this messenger appears to be the major one responsible for the smooth muscle cell hyperpolarization in the relaxation elicited by ACh, which is mediated by activation of the Na+ pump and ChTx- and 4-AP-sensitive K+ channels, likely BK(Ca) and Kv channels.

Acetylcholine↗

PubMed1999

Structural and functional characterization of an epitope in the conserved C-terminal region of HIV-1 gp120.

Through an integrated study of the reactivity of a monoclonal antibody, 803-15.6, with synthetic peptides and native recombinant HIV-1 envelope glycoprotein gp120, we have obtained structure-functional information on a region of rgp120 not yet elucidated by X-ray crystallography. mAb 803-15.6 binds with high affinity and broad cross-clade specificity to the conserved C-terminal region (amino acids 502-516) of HIV-1 rgp120. Phage display selection from a random peptide library identified the core binding motif as AXXKXRH, homologous to residues 502-508. Using quantitative binding analyses, the affinity of mAb 803-15.6 for native, monomeric recombinant gp120HXB2 (rgp120) was found to be similar to that for the synthetic gp120 peptide (502-516). Circular dichroism studies indicate that the synthetic peptide largely has a random coil conformation in solution. The results therefore suggest that the 803-15.6 epitope is fully accessible on rgp120 and that this region of rgp120 is as flexible as the synthetic peptide. Residues 502-504 are on the edge of a putative gp41 binding site that has been postulated to change conformation on CD4 binding. However, the affinity of mAb 803-15.6 for rgp120 is not affected by binding of CD4 and vice-versa. These results suggest either that the 502-504 region does not change conformation upon CD4 binding, or that recombinant gp120 does not undergo the same changes as occur in the native viral gp120-gp41 oligomer. The detailed characterization of the 803-15.6 epitope may be useful for further study of the role of the C5 region of gp120 in the viral attachment and fusion process.

Amino Acid Sequence↗

PubMed1999

Selection of gp41-mediated HIV-1 cell entry inhibitors from biased combinatorial libraries of non-natural binding elements.

The trimeric, alpha-helical coiled-coil core of the HIV-1 gp41 ectodomain is thought to be part of a transient, receptor-triggered intermediate in the refolding of the envelope glycoprotein into a fusion-active conformation. In an effort to discover small organic inhibitors that block gp41 activation, we have generated a biased combinatorial chemical library of non-natural binding elements targeted to the gp41 core. From this library of 61,275 potential ligands, we have identified elements that, when covalently attached to a peptide derived from the gp41 outer-layer alpha-helix, contribute to the formation of a stable complex with the inner core and to inhibition of gp41-mediated cell fusion.

Amino Acid Sequence↗

PubMed1999

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats.

The aim of the present study was to assess the alterations in cardiac Ca2+ homeostasis induced by hypertension using electrically paced right ventricular strips from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2 Basal contractile force was higher in SHR than in WKY. Similarly, the beta-adrenoceptor agonist isoprenaline (10 nM-10 microM) induced a concentration-dependent positive inotropic effect that was higher in SHR than in WKY, which was in turn inhibited by the beta-adrenoceptor antagonist propranolol (1 microM) in both strains. 3 Preincubation of strips with the L-type Ca2+ channel blockers, nifedipine (1 microM) or verapamil (10 microM), markedly inhibited the isoprenaline response, the inhibition being higher in SHR than in WKY. However, this inhibition was minor by the T-type Ca2+ channel blocker mibefradil (10 microM). 4 Bay K 8644 (10 nM-10 microM), a L-type Ca2+ channel activator induced a concentration-dependent positive inotropic effect, that was greater in SHR than WKY. 5 Nifedipine and verapamil (both 0.1 nM-10 microM) inhibited in a concentration-dependent way the inotropic effect induced by 0.3 microM isoprenaline or 1 microM Bay K 8644. The inhibition was higher in SHR than in WKY. Mibefradil (0.1 nM-10 microM) only clearly inhibited the isoprenaline and Bay K 8644 inotropic effects at 10 microM in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 nM-10 microM), was a more effective depressor of isoprenaline-induced response in SHR than in WKY. 7 These results suggest that cardiac Ca2+ homeostasis in SHR ventricular strips is altered compared with those of WKY, showing an increased Ca2+ entry through L-type Ca2+ channels and release from sarcoplasmic reticulum; the participation of T-type Ca2+ channels are irrelevant in this tissue.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1999

Peptide ligands to human immunodeficiency virus type 1 gp120 identified from phage display libraries.

We have used phage-displayed peptide libraries to identify novel ligands to the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120. Screening of libraries of random 12-mers, 7-mers, and cyclic 9-mers produced two families of gp120 binding peptides. Members of a family with the prototype sequence RINNIPWSEAMM (peptide 12p1) inhibit the interaction between gp120 and both four-domain soluble CD4 (4dCD4) and monoclonal antibody (MAb) 17b, a neutralizing antibody that covers the chemokine receptor binding surface on gp120. Peptide 12p1 inhibits the interaction of 4dCD4 with gp120 from three different HIV strains, implying that it binds to a conserved site on gp120. Members of a second family of peptides, with the prototype sequence TSPYEDWQTYLM (peptide 12p2), bind more weakly to gp120. They do not detectably affect its interaction with 4dCD4, but they enhance its binding to MAb 17b. A common sequence motif in the two peptide families and cross-competition for gp120 binding suggest that they have overlapping contacts. Their divergent effects on the affinity of gp120 for MAb 17b may indicate that their binding stabilizes distinct conformational states of gp120. The functional properties of 12p1 suggest that it might be a useful lead for the development of inhibitors of HIV entry.

Amino Acid Sequence↗

PubMed1999

Gender differences in the endothelial regulation of alpha2-adrenoceptor-mediated contraction in the rat aorta.

The aim of this study was to determine the possible influence of sex hormones on the contractile responses induced by clonidine, an agonist of alpha2-adrenoceptors, as well as the endothelial modulation of these responses. For this purpose, thoracic aorta segments from male (control and castrated) and female (in oestrous phase and ovariectomized) rats were used. In intact segments from the four groups of rats, clonidine (0.01-10 micromol/l) induced concentration-dependent contractions, which were increased by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (0.1 mmol/l) or by endothelium removal, but were reduced by 1 micromol/l yohimbine (an alpha2-adrenoceptor antagonist) in all animals and by 1 micromol/l indomethacin (a cyclo-oxygenase inhibitor) in control males only. The rank order of the magnitude of the maximal response was: oestrous females>ovariectomized females>control males>castrated males, whereas the sensitivity to clonidine (EC50 value) was similar in all animals. In endothelium-denuded segments, the rank order was: oestrous females=control males>ovariectomized females=castrated males. These results suggest that: (1) the presence of oestrogen or androgen increases the contraction caused by alpha2-adrenoceptor activation with clonidine; (2) endothelium negatively modulates the response to this agonist in the four groups of rats, due to endothelial NO release (entirely in females and in part in males); (3) androgen also seems to modulate the response by stimulating the release of an endothelial contracting factor, probably a prostanoid; and (4) the endothelium of males has a greater capacity than that of comparable females for negative regulation of the tension generated by the underlying vascular smooth muscle.

Adrenergic alpha-Agonists↗