DA1 receptors modulation in rat isolated trachea.

We have previously demonstrated that low dose of inhaled dopamine (0.5-2 microg kg(-1) min(-1)) induces broncodilatacion in patients with acute asthma attack, suggesting that this dopamine effect is mediated by dopaminergic rather than by adrenergic receptors. To understand better these dopamine effect, rat tracheal smooth muscle was used as a model to evaluate the responses of beta2-, alpha1-, alpha2-adrenergic and DA1 and DA2 dopaminergic antagonists. Tracheal rings from male Sprague-Dawley rats (n = 90) were excised and placed in an organ bath containing modified Krebs-Ringer bicarbonate buffer at 37 degrees C, and gassed with O2 (95%) and CO2 (5%). Contractile responses were recorded with an isometric transducer in a polygraph (Letica, Spain). Contraction was induced by accumulative doses of acetylcholine (0.1, 0.3, 1, 3, 10 mM) or by electric field stimulation (10 Hz at 2 milliseconds), and accumulative doses of dopamine were added to the bath. Low concentration (0.1-0.3 mM) elicited a small initial contraction, followed by a marked relaxation. Cholinergic contraction was completely reversed at 6 mM of dopamine. This biphasic dopaminergic response was not blocked by incubation with beta2-adrenergic antagonist propranolol (0.1 microM), alpha1-antagonist, terazosin (0.1 mM), alpha2-antagonist, yohimbine (0.1 mM), or by DA2 antagonist metoclopramide (1-8 mM); DA1 antagonist SCH23390 (0.1 microM) produced a sustained increase of basal tone but did not block initial dopaminergic contraction and partially inhibited bronchodilator effect of dopamine. Dopaminergic relaxation in rat trachea is mediated by DA1 rather than by DA2 receptors; and adrenergic receptors are not involved in such dopamine-induced response. Finally, DA1 antagonist SCH23390 exerts intrinsic contractile activity on airway smooth muscle that deserves further research.

The actions of dopamine on the airways.

BACKGROUND: Dopamine exerts inhibitory and excitatory effects on different systems. In the lungs, dopamine modulates respiratory functions through carotid bodies and modulates pulmonary blood vessel tone, alveolar liquids, and bronchial exchange, and possibly participates in the regulation of airways diameter. It has been reported that dopamine has no acute effect on human airways in normal subjects or those with asthma background. However, inhaled or infused dopamine decreased histamine-induced bronchoconstriction in both normal and asthmatic subjects. We have examined the possible modulating effect of dopamine on bronchial diameter by administering inhaled dopamine and the DA2 dopaminergic blocker metoclopramide to subjects with various degrees of bronchial tone. METHODS: We examined 56 volunteers. Arterial blood pressure and heart rate were determined in every subject. By means of spirometry, we measured forced vital capacity, forced expiratory volume in the first second, maximal forced expiratory flow, and forced expiratory flow at 50% of vital capacity, before and after each treatment. By inhalation with a nebulizer, we administered dopamine (0.5 microg/kg/min) to 10 healthy subjects, 10 subjects with asthma without acute bronchospasm, and 16 subjects with acute asthma attack; intravenous metoclopramide (7 microg/kg/min) was administered to 10 healthy subjects and 10 subjects with asthma without acute bronchospasm. For ethical reasons, metoclopramide was not used in subjects with acute asthma attack. STATISTICS: non-parametric Wilcoxon tests for paired samples, ANOVA tests, and Bonferroni multiple comparison tests were performed. RESULTS: Inhaled dopamine increased forced expiratory volume in the first second, forced vital capacity, maximal forced expiratory flow, and forced expiratory flow at 50% of vital capacity in the acute asthma attack group, but there were no modifications in the healthy group or in the asthma without acute bronchospasm group. Metoclopramide did not induce changes in respiratory parameters in healthy individuals or in those with asthma without acute bronchospasm. CONCLUSIONS: Inhaled dopamine was able to induce bronchodilatation when the bronchial tone was already increased by acute asthma attack, but it did not modify the resting bronchial tone in normals or in asthmatics without acute bronchospasm. DA2 blockade with metoclopramide did not modify resting bronchial tone either. We suggest that dopamine exerts a modulatory effect on bronchial tone of human airways depending on the degree of existing basal tone.

Dopaminergic receptors: a new antihypertensive mechanism.

The neutrotransmitter dopamine, precursor of noradrenaline, induces a variety of cardiovascular and renal physiological responses, including an increase in myocardial contractility and cardiac output without changes in heart rate, passive and active vasodilatation, diuresis and natriuresis. These responses result from its interaction with the dopamine receptors D1, D2, D3, D4 and D5. In addition, recent findings suggest the existence of D6 and D7 receptors. In some types of hypertension dopamine is known to influence the control of arterial pressure by influencing the central and peripheral nervous system and target organs such as the kidneys and adrenal glands. Since dopamine and its derivatives have been shown to have antihypertensive effects, it is important to review the physiological and pharmacological aspects of dopamine and its receptors, and the clinical uses that they could have in the therapy of arterial hypertension.

Desarrollo del conocimiento científico biológico y social en la teoría y la práctica de la salud de los trabajadores / Development of the scientific biological and social knowledge in the theory and practice of the occupational health

La búsqueda de soluciones efectivas reclaman un personal de salud con una sólida formación teórica y metodológica en ciencias biológicas y en ciencias sociales, que les permita abordar en forma integrada los problemas concretos e incorporarse eficazmente a equipos de trabajo multidisciplinarios. En ese sentido, este artículo, plantea develar las relaciones entre el desarrolo del conocimiento científico, en sus vertientes biológica y social, en un área del conocimiento relativamente nueva y marginada, como lo es la salud de los trabajadores.