Browsing by Author "Miranda, R"

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    A2B adenosine receptor mediates human chorionic vasoconstriction and signals through arachidonic acid cascade
    (2005) Donoso, MV; López, RL; Miranda, R; Briones, R; Huidobro-Toro, JP
    Because adenosine is a vascular tone modulator, we examined the effect of adenosine and congeners in the vascular reactivity of isolated human placental vessels and in perfused cotyledons. We characterized its vasomotor action and tentatively identified the receptor subtypes and their intracellular signaling mechanisms. We recorded isometric tension from the circular layer of chorionic vessel rings maintained under 1.5 g of basal tension or precontracted with KCl. The relative order of potency of adenosine and structural analogs is consistent with the expression of A2B receptors, 5'-(N-ethylcarboxamido) adenosine (NECA) being the most potent. The maximal contraction ranged from 45% to 60% of the KCl standard response, except for an A(2A) receptor agonist that did not exceed 15%. Consistently, NECA was 100-fold more potent than adenosine to raise the perfusion pressure of ex vivo perfused cotyledons. In contrast, a selective A(3) receptor agonist relaxed precontracted rings of chorionic vessels. Whereas a selective A3 receptor antagonist was ineffective to antagonize adenosine-induced contraction, A(2) or A(1) receptor antagonists reduced adenosine-induced vasoconstriction concentration-dependently. Denudation of the endothelial layer reduced adenosine- and NECA-induced contractions by 50-70%. Furthermore, indomethacin reduced adenosine- or NECA-induced contractions concentration-dependently in intact and endothelium-denuded rings. A thromboxane receptor antagonist blocked adenosine- and NECA-induced contractions in intact and endothelium-denuded rings, suggesting the involvement of an arachidonic acid metabolite as the mediator of the vasoconstriction. We propose that adenosine A(2B) receptors mediate the adenosine- induced contraction vasomotor effect in human chorionic vessels and that this involves synthesis of a thromboxane receptor activator or a related prostanoid.
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    Dynamic mechanical and dielectric relaxations of poly(difluorobenzyl methacrylates)
    (WILEY-BLACKWELL, 2000) Diaz Calleja, R; Sanchis, MJ; Saiz, E; Martinez Pina, F; Miranda, R; Gargallo, L; Radic, D; Riande, E
    This work reports the mechanical and dielectric relaxation spectra of three difluorinated phenyl isomers of poly(benzyl methacrylate), specifically, poly(2,4-difluorobenzyl methacrylate), poly(2,5-difluorobenzyl methacrylate) and poly(2,6-difluorobenzyl methacrylate). The strength of the dielectric glass-rubber relaxation of the 2,6 difluorinated phenyl isomer is, respectively, nearly three and two times larger than the strengths of the 2,5 and 2,4 isomers. The 2,4 isomer presents a mechanical ct peak the intensity of which is nearly two times that of the other two isomers. Both the mechanical and dielectric relaxation spectra display a subglass process, called gamma relaxation, centered in the vicinity of -50 degrees C at 1 Hz and, in some cases, a subglass beta absorption is detected at higher temperature partially masked by the glass-rubber relaxation. The mean-square dipole moments per repeating unit, [mu 2]/x, measured at 25 degrees C in benzene solutions, are 2.5 D-2, 1.9 D-2, and 5.0 D-2 for poly(2,4-difluorobenzyl methacrylate), poly(2,5-difluorobenzyl methacrylate) and poly(2,6-difluorobenzyl methacrylate), respectively. These results, in conjunction with Onsager type equations, permit to conclude that auto and cross-correlation contributions to the dipolar correlation coefficient may have the same time-dependence. On the other hand, dipole intermolecular interactions, rather than differences in the flexibility of the chains, seem to be responsible for the relatively high calorimetric glass-transition temperature of the 2,6 diphenyl isomer, which is, respectively, nearly 36 degrees C and 32 degrees C above the T-g's of the 2,4 and 2,5 isomers. Molecular Mechanics calculations give a good account of the differences observed in the polarity of the polymers. (C) 2000 John Wiley & Sons, Inc.
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    Neuropeptide Y is released from human mammary and radial vascular biopsies and is a functional modulator of sympathetic cotransmission
    (2004) Donoso, MV; Miranda, R; Irarrázaval, MJ; Huidobro-Toro, JP
    The role of neuropeptide Y (NPY) as a modulator of the vasomotor responses mediated by sympathetic cotransmitters was examined by electrically evoking its release from the perivascular nerve terminals of second- to third-order human blood vessel biopsies and by studying the peptide-induced potentiation of the vasomotor responses evoked by exogenous adenosine 5' triphosphate (ATP) and noradrenaline (NA). Electrical depolarization of nerve terminals in mammary vessels and radial artery biopsies elicited a rise in superfusate immunoreactive NPY (ir-NPY), which was chromatographically identical to a standard of human NPY (hNPY); a second peak was identified as oxidized hNPY. The amount released corresponds to 4-6% of the total NPY content in these vessels. Tissue extracts also revealed two peaks; hNPY accounted for 68-85% of the ir-NPY, while oxidized hNPY corresponded to 7-15%. The release process depended on extracellular calcium and on the frequency and duration of the electrical stimuli; guanethidine blocked the release, confirming the peptide's sympathetic origin. Assessment of the functional activity of the oxidized product demonstrated that while it did not change basal tension, the NA-evoked contractions were potentiated to the same extent as with native hNPY. Moreover, NPY potentiated both the vasomotor action of ATP or NA alone and the vasoconstriction elicited by the simultaneous application of both cotransmitters. RT-PCR detected the mRNA coding for the NPY Y-1 receptor. In summary, the release of hNPY or its oxidized species, elicited by nerve terminal depolarization, coupled to the potentiation of the sympathetic cotransmitter vasomotor responses, highlights the modulator role of NPY in both arteries and veins, strongly suggesting its involvement in human vascular sympathetic reflexes. Copyright (C) 2004 S. Karger AG, Basel.
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    Synthesis, dilute solution properties, and chain flexibility of poly(difluorobenzyl methacrylates)
    (MARCEL DEKKER INC, 2000) Gargallo, L; Miranda, R; Radic, D
    The synthesis and dilute solution behavior of poly(2,5-difluorobenzyl methacrylate) (P2,5-DFBM) and poly(2,6-difluorobenzyl methacrylate) (P2,6-DFBM) are described. The polymers were characterized by viscosity and classical lightscattering and size exclusion chromatography (SEC) measurements. The Kuhn-Mark-Houwink-Sakurada (KMHS) relationships were established. Unperturbed dimensions (1/2), the rigidity factor sigma, the characteristic ratio C-infinity and the thermodynamic parameters were determined using the Stockmayer-Fixman treatment. The double substitution in the 2,5 and 2,6 positions by fluorine atoms increases the conformational parameters. The presence of substituents such as -CH3 or fluorine atoms close to the main chain (2,6 position) affects the internal rotation potential in the same way.