RESUMO
The diastolic pulsatile increase in arterial blood pressure is shown to occur earlier in the aorta than in other arteries. It is thus not a reflection of the systolic pressure wave, as has been generally assumed, but an independent pressure wave produced by the sequential contraction of the arterial tree. Conversely, a systolic pulsatile decrease in the rate of blood pressure rise is also produced by an active relaxation of the arterial tree. Simultaneously with the pulsatile changes in arterial blood pressure, there are corresponding changes in arterial blood flow. All these cyclic changes are reflex responses to decreasing diastolic and increasing systolic baroreceptor firing rates, respectively. The two reflexes contribute, together with the known compliance of the large arteries and the great arteriolar blood flow resistance, to the steadiness of capillary blood flow throughout the systolic and the much longer-lasting diastolic phases of the cardiac cycle.
Assuntos
Pressão Arterial/fisiologia , Artérias/fisiologia , Barorreflexo/fisiologia , Modelos Cardiovasculares , Fluxo Pulsátil/fisiologia , Sístole/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Simulação por Computador , HumanosRESUMO
The concept of hormones as chemical messengers that transmit information from one organ to other organs by way of circulating blood has implications that have not been made explicit. In this paper the concept is analyzed and is shown to be inconsistent with many observations. The previously proposed concepts of hormone multifunctionalities, hormonal multisignal messages, and the conversion of hormones into other hormones are shown to clarify conflicting observations as well as the congruous mode of functioning of endocrine systems with multifunctional hormones. A strategy is proposed for identifying the compositions and functions of the diverse multisignal messages conveyed by any hormone. The information so obtained could be useful for the development of more selective hormonal therapies.
Assuntos
Sistema Endócrino/fisiologia , Hormônios/fisiologia , HumanosRESUMO
A theory is presented outlining how organisms can function and benefit from multifunctionality of hormones in order to enhance greatly the information-carrying potential of endocrine signaling. Hormones are produced continuously as micropulses, and intermittently as larger pulses. It is generally believed that micropulses generate fluctuating basal hormone concentrations, which may consistently elicit particular responses among diverse variables. Evidence is discussed suggesting that in contrast to the hormone micropulses, the larger endogenous hormone pulses may elicit responses which may differ from one pulse to another and may therefore serve different physiological functions. In this paper we postulate that an endogenous hormone pulse is a specific form of a multisignal message that serves a certain physiological function. Different pulses of a hormone may be signals of diverse multisignal messages that serve different functions. A multisignal message may elicit congruous responses by selectively enhancing some actions and suppressing other actions of the component signals. Various roles of signals of multisignal messages are discussed, as well as processes that may be involved in the diversity and selectivity of actions of different pulses of a hormone. Hormones also are converted into other hormones; we analyze how precursor and derived hormones may function independently of each other, and how precursor hormones may give rise to permissive effects. Mechanisms involved in therapeutic and adverse effects of hormone administrations are analyzed, and a strategy is suggested for developing more selective hormonal therapies.
Assuntos
Comunicação Celular/fisiologia , Sistema Endócrino/fisiologia , Homeostase/fisiologia , Hormônios/metabolismo , Modelos Biológicos , Animais , Glândulas Endócrinas/metabolismo , Retroalimentação/fisiologia , Hormônios/sangue , HumanosRESUMO
This study determined the in vitro effects of 4-hydroxycoumarin (4-HC) employing the melanoma cell line B16-F10 and the non-malignant fibroblastic cell line B82. 4-HC disorganized the actin cytoskeleton in B16-F10 cells, but not in B82 fibroblasts. Cytoskeletal disorganization correlated with reductions in cell adhesion to four extracellular matrix proteins and inhibition of random motility. 4-HC did not modify cell viability or actin expression, but decreased tyrosine phosphorylation of several proteins in melanoma cells. Because adhesion of tumor cells to extracellular matrix is required during the metastatic process, 4-HC might be useful as an adjuvant therapy for melanoma.
Assuntos
4-Hidroxicumarinas/farmacologia , Actinas/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Proteínas da Matriz Extracelular/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoesqueleto/ultraestrutura , Proteínas da Matriz Extracelular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Melanoma Experimental/fisiopatologia , Camundongos , Proteínas de Neoplasias/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fosfotirosina/metabolismo , Células Tumorais CultivadasRESUMO
Recientemente se han demostrado correlaciones significativas entre la expresión de algunas moléculas de adhesión y la capacidad de células de producir metástasis. Por ejemplo, se ha observado una correlación entre la expresión de la integrina a6/ß1 en células cancerosas pulmonares y la producción de metástasis. También se ha observado correlación entre la expresión de algunas moléculas de adhesión en células de melanoma maligno y su capacidad de producir metástasis pulmonares. En este trabajo estudiamos la acción in vitro de la cumarina en el melanoma murino B16-F10, productor de metástasis pulmonares, sobre la expresión de dos moléculas de adhesión, ICAM-1 y LFA-1. No se observó disminución en la expresión de la molécula de adhesión LFA-1, y la expresión de ICAM-1 disminuyó de manera uniforme con todas las concentraciones de cumarina estudiadas. Estos resultados no explican los efectos antimetastásicos producidos por la cumarina en modelos animales de metástasis pulmonares experimentales y espontáneas, ni los efectos antimetastásicos en humanos. Es necesario, por tanto, estudiar el efecto de la cumarina en la expresión de otras integrinas. Este tipo de estudios permite el desarrollo de nuevas estrategias en la búsqueda de mejores agentes antineoplásicos que disminuyan en mayor grado el número y tamaño de metástasis, y retarden importantemente su producción; contribuye, adenomás, al conocimiento de la fisiopatogenia de estos tumores malignos