ABSTRACT
After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.
Subject(s)
Humans , Boron Compounds/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/metabolism , RNA, Messenger/genetics , Umbilical Arteries/drug effects , Vascular Capacitance/drug effects , Blotting, Western , Cells, Cultured , Calcium Channel Blockers/pharmacology , Calcium Channels/chemistry , Calcium Channels/genetics , Calcium Channels/metabolism , Calcium/metabolism , Histamine Agonists/pharmacology , Histamine/pharmacology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Muscle, Smooth/cytology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Sarcoplasmic Reticulum/drug effects , Sarcoplasmic Reticulum/metabolism , Serotonin Receptor Agonists/pharmacology , Serotonin/pharmacology , TRPC Cation Channels/genetics , TRPC Cation Channels/metabolism , Umbilical Arteries/cytology , Umbilical Arteries/metabolismABSTRACT
El fumar tabaco durante el embarazo aumenta los riesgos en la salud materno-infanto juvenil provocando múltiples alteraciones atribuidas a la nicotina y al monóxido de carbono producidos por el cigarrillo.
Subject(s)
Pregnancy , Placenta , Pregnancy , Serotonin , Tobacco , Umbilical ArteriesABSTRACT
La vena safena humana (VSH) se utiliza como puente en la cirugía de revascularización coronaria y de otros lechos arteriales, especialmente de miembros inferiores. Dado que los puentes de VSH presentan un porcentaje considerable de obliteración, numerosos estudios han investigado los factores que promoverían la producción de la estenosis en los mismos. Este artículo describe resultados sobre las condiciones estructurales y funcionales que confluyen para producir la obstrucción de los puentes de VSH. Se analiza la reactividad de la VSH a agonistas fisiológicos, incluídos los factores contrayentes y relajantes derivados del endotelio, por su importancia en determinar el vasoespasmo y en modificar la expresión de factores de crecimiento tisular y/o promotores de procesos trombóticos y ateromatosos. Se describen mecanismos involucrados en la regulación del estado contráctil de los miocitos lisos, en particular la actividad de canales de K+ de la membrana
Subject(s)
Humans , Coronary Artery Bypass/methods , Saphenous Vein/anatomy & histology , Saphenous Vein/physiology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Potassium Channels/physiology , Saphenous Vein/drug effectsABSTRACT
This work includes results on chronotropic, inotropic and lusitropic changes induced by capsaicin on isolated rat atria. As regards spontaneous frequency, it was stimulated from 10(-9) M up to 7 x 10(-7) M of capsaicin. A simultaneous depression in developed force (F) showed a signigicant correlation with this positive chronotropic effect up to 7 X 10(-8) M of capsaicin, which is the result of the negative staircase phenomenon in the rat heart. The correlation was lost at 2 and 7 x 10(-7) M of capsaicin since in spite of the sustained increase in atrial rate the decrease in F was reversed and then depressed again at 2 and 7x 10(-6) M of capsaicin without changes in frequency. A concentration of capsaicin that overcome the negative staircase phenomenon, 5 x 10(-7) M, was tested as unique dose resulting in stimulation of the chronotropic, inotropic and lusitropic states of the atria. Percentual differences with respect to control values were maximal after 1-3 minutes for frequency (10+3 per cent), F (29+4 per cent), maximal velocity of force development (+F=50+12 per cent) (in all cases +F and -F,bold indicates +F and -F, respectively) and maximal velocity of relaxation (-F=64+13 per cent); a positive lusitropic effect was significant after 8-10 minutes (+F/-F=-17+7 per cent). Capsaicin did not affect the rat atria in the presence of 10(-6) M of ruthenium red, a blocker of capsaicin activation of sensory nerves, indicating that the stimulatory effects were entirely mediated by the release of neurotransmitters and that this concentration of capsaicin was not deleterous "per se". Capsaicin elicited similar inotropic responses in electrically driven isolated atria (+F=41+9 per cent) but the positive lusitropic effect was lost suggesting that capsaicin-induced increases in -F are limited at a frequency higher than the spontaneous frequency (11+6 vs. 32+4 per cent, respectively). 10(-6) M of CGRP8(-37), an antagonist of CGRP1 receptors, suppress the stimulatory effects of capsaicin on atrial contraction. In summary, atrial rate as compared to atrial contraction is more sensitive to the neurotransmitter released by capsaicin, which results in mechanical effects expressing the negative staircase phenomenon in the rat at low concentrations of capsaicin. The positive chronotropic, inotropic and lusitropic responses elicited by capsaicin are mediated by the reelease of neurotransmitters from sensory fibbers and no deletereous effects...
Subject(s)
Animals , Male , Rats , Capsaicin/pharmacology , Heart Atria/drug effects , Heart Rate/drug effects , Myocardial Contraction/drug effects , Receptors, Calcitonin Gene-Related Peptide/analysis , Capsaicin/analysis , Heart Atria/chemistry , Rats, Sprague-Dawley , Ruthenium Red , Stimulation, ChemicalABSTRACT
La insulina afecta mecanismos fisiológicos generales que regulan la presión arterial, y a nivel celular modifica las funciones del endotelio y del mosculo liso vascular, que son determinantes de la resistencia periférica. Describimos los efectos de la preincubación con insulina (40 muU/ml, durante 1-2 hs) sobre la reactividad contráctil de anillos intactos de aorta de rata y sobre la captaci>n de 45Ca2+ en segmentos de aorta de rata hipermeabilizados por tratamiento con EGTA. La preincubación con insulina no afectó las contracciones inducids por 1 muM de NA, ni la relajación de las mismas inducida por 10 mM de cafeína. La respuesta contractil a 1 muM de Ang-II (que en la aorta de rata es independiente de endotelio) fue estimulada por la preincubación con insulina en la fuerza máxima desarrollada y en la velocidad de relajación espontánea de la contracción. La diferencia en la captación de 45Ca2+ en RS entre los segmentos de aorta tratados y no tratados con insulina fue mayor a los 5 minutos con respecto a la medida a los 30 minutos. Se concluye que la preincubación con insulina afecta en forma directa la respuesta mecánica del mosculo liso aórtico estimulado con Ang-II y se propone a la modificación de la actividad del RS como uno de los mecanismos mediante el cual la insulina participa en la regulación del Ca2+ citosólico.