Actividad rítmica espontánea en vasos de placenta humana: ¿un marcapaso fisiológico en los vasos sanguíneos? / Spontaneous rhythmic contractions of human umbilical vessels, evidences for a physiological pacemaker in blood vessels?

Background: Placental vessels are not innervated. Therefore the vasomotor activity and vascular tone is not regulated by the nervous system. Aim: To assess the existence of pacemaker mechanisms related to rhythmic motor activity of blood vessels. Material and methods: Isometric contractions of rings from umbilical and chorionic vessels of term human placentas were monitored. Results: Recordings of the circular layer of chorionic and umbilical vessels revealed rhythmic spontaneous contractions with a frequency of 1,4ñ0,05 cycles/min, the duration of each cycle was 42,8ñ0,24 s (n=12). The amplitude of contractions was larger in veins than in arteries, predominating in umbilical vein biopsies, proximal to the fetus. Both the frequency and the amplitude of contractions were relatively constant during the first 30 min. However, after an hour, the frequency declined while the amplitude increased. The absence of the endothelium neither modified the frequency nor the amplitude of the rhythmic activity. Blockage of voltage dependent sodium channels or calcium channels did not alter the frequency of spontaneous contractions, although their magnitude was reduced. Glibenclamide, an ATP-dependent K+ channel blocker or the blockade of gap junctions ablated the frequency and amplitude of spontaneous contractions. Conclusions: We propose that rhythmic contractions are triggered by pacemaker cells located in the circular layer of the smooth muscle of blood vessels and spread via gap junctions; they likely contribute to the control of blood flow

Contribución del neuropéptido Y a la fisiología de la co-transmisión simpática humana: estudios en biopsias de vena safena / Neuropeptide Y contribution to the physiology of human sympathetic cotransmission: studies in saphenous vein biopsies

Background: It is known that the sympathetic varicosities co-store and co-release norepinephrine (NE) together with adenosine S-triphosphate (ATP) and neuropeptide Y (NPY). Aim: To describe the chemical characterisation of stored and released NPY from the varicosities of sympathetic nerve terminals surrounding segments of the human saphenous vein, and the vasomotor activity of rings electrically depolarized or contracted by the exogenous application of the co-transmitters. Material and methods: Saphenous vein tissues were obtained from patients undergoing elective cardiac revascularization surgery. Results: The chromatographic profile of NPY extracted from biopsies is identical to a chemical standard of human NPY. Upon electrical depolarisation of the perivascular sympathetic nerve terminals, we demonstrated the release of NPY to the superfusion media, which did not exceed a 1percent of its stored content. The release of the peptide is sensitive to guanethidine, and to extracellular calcium, suggesting that the mechanism of its release is exocytotic in nature. The electrically evoked release of NPY is dependent on the frequency and duration of the electrical pulses. Phenoxybenzamine reduces the electrically evoked release of NPY. Exogenous application of NE and ATP contract saphenous vein rings; the simultaneous application of NE plus ATP causes a synergic response, effect which is further potentiated by the joint co-application of 10 nM NPY. Conclusions: Present results highlight the role of NPY as a sympathetic co-transmitter in the regulation of human vascular tone

Liberación de neuropéptido tirosina (NPY) de los terminales nerviosos en vasos mamarios / Liberation of tyrosine neuropeptide (NPY) from mammary vessels nerve endings

En este estudio caracterizamos la liberación de NPY de biopsias de la arteria y vena mamaria. Se induce la liberación de los neurotransmisores por medio de despolarización eléctrica de los nervios simpáticos perivasculares. Con estímulo de 70 V, 0,5 msec, 40 Hz por 5 min, segmentos de la arteria mamaria liberan 17,7 ñ 6,7 fmol (n=4) de NPY, la vena libera 4,3 ñ 1,5 fmol (n=4), valores que corresponden a un 1-2 por ciento del NPY en la biopsia. El NPY liberado por estímulo eléctrico no es metabolizado en la sinapsis neuroefectora. La liberación del NPY al medio de superfusión tiene un curso temporal lento, la máxima liberación ocurre a los 10 min del estímulo. La liberación del NPY es dependiente de la duración del estímulo (coeficiente de correlación = 0,647, p<0,01); y de la frecuencia de estimulación (coeficiente de correlación = 0,611, p<0,05), indicando que la liberación es un proceso controlado por la frecuencia de la descarga y por la intensidad del estímulo simpático vasomotor. El proceso de liberación es dependiente del calcio, ya que en ausencia de calcio extremo, la liberación de NPY se reduce en 78 por ciento. El NPY actúa sobre receptores postsinápticos, donde produce un efecto facilitador significativo de la acción vasomotora de NA y ATP. En conclusión, NPY se libera al espacio sináptico por exocitosis, donde participa junto a NA y ATP en la regulación del tono vasomotor simpático

Aspectos morfo-funcionales de arterias y venas mamarias usadas en revascularización cardíaca / Morphologic and functional aspects of mammary arteries and veins used for myocardial revascularization surgery

Los vasos sanguíneos están inervados por el sistema nervioso simpático autonómico. La fisiología y neuroquímica de los nervios perivasculares humanos ha sido poco estudiada. Con el propósito de contribuir a las investigaciones sobre la fisiología de la co-transmisión simpática humana, esta investigación se concentró en: i) estudiar el contenido de los neurotransmisores simpáticos, noradrenalina (NA) y neuropéptido y (NPY) en vasos de arteria y vena mamaria interna humana; ii) detectar mediante técnicas inmunohistoquímicas la presencia de los nervios simpáticos perivasculares de estos vasos; iii) caracterizar la reactividad vascular de la arteria mamaria interna, como un modelo usado en implantes de revascularización cardíaca. Se estudió además, la vena mamaria derivada de la misma biopsia. La arteria y vena mamaria contienen 50 veces más NA que NPY, el contenido de NA y NPY en la arteria y en la vena es muy similar. La detección inmunohistoquímica de los nervios simpáticos demuestra que éstos se localizan entre las capas musculares de los vasos. La estimulación de los filetes nerviosos perivasculares produce respuestas vasomotoras sensibles a tetrodotoxina y guanetidina, lo que es consistente con la naturaleza simpática de la respuesta, confirmando que parte de los nervios perivasculares son simpáticos. Los músculos lisos se estimulan por NA y por ATP, que sólo no contrae, facilita las respuestas vasomotoras de la NA. Estos resultados permiten concluir que en la arteria y la vena mamaria interna humana NA, ATP y NPY cooperan en la respuesta vasomotora, evidenciando la co-transmisión simpática en humanos

Benzodiazepinas, reguladores alostéricos del receptor GABA-A: alcances fisiológicos, farmacológicos y terapéuticos / Benzodiazepines, allosteric modulators of GABA-A receptor: physiologic, pharmacologic and therapeutic features

The molecular basis underlying the anxiolytic, sedative hypnotic properties of the benzodiazepine compounds are examined at the ligh of recent progress in the field of psychopharmacology and molecular biology. The benzodiazepine receptors, originally characterized as the building site of radiolabelled benzodiazepines, are now identified as allosteric domains of a small population of the plethora of putative brain GABA-A receptor complexes. Emphasis is given to the understanding of the molecular biology of the GABA-A receptor complex and the hypothesis of the multiplicity of benzodiazepine receptors. Experiments describing the need of the gamma subunit of the GABA-A receptor for full benzodiazepine action as positive or negative allosteric modulators of the GABA-A receptor complez are analyzed. Likewise, experiments differentiating the barbiturate receptor from that of the benzodiazepines, alcohol and anesthetic agents are discussed ath the light of recent progress in the molecular biology of the GABA-A receptor. It is concluded that the GABA-A receptor complex is regulated at multiple sites, by a variety of drugs. Regarding putative endogenous ligands for the benzodiazepine receptor, evidences are discussed in support of the endozepines and their implications in health and diseases