Papel de la adrenomedulina en el control de la presión arterial y la homeostasis del líquido extracelular

La adrenomedulina es un péptido de 52 aminoácidos recientemente identificado que presenta un efecto vasodilatador potente y prolongado, así como una acción diurética y natriurética a nivel renal. El efecto vasodilatador de la adrenomedulina está mediado por un aumento de los niveles intracelulares de AMP cíclico, así como por un aumento de la síntesis de óxido nítrico. Los efectos diurético y natriurético de este péptido son debidos tanto a sus acciones sobre el flujo sanguíneo renal como sobre la función tubular. Además, la adrenomedulina inhibe la secreción de aldosterona estimulada por angiotensina, tiene un efecto inotrópico positivo sobre el miocardiocito, inhibe la proliferación y migración de la fibra muscular lisa vascular, y a nivel cerebral inhibe la sed y el apetito por la sal. La expresión de este péptido se ha demostrado en muchos tejidos, pero es especialmente prominente en células endoteliales. Por ello se cree que la producción de este péptido en las células endoteliales, regulada por el estrés de cizallamiento (flujo), citoquinas o neurohormonas, actúa de forma paracrina en la fibra muscular lisa subyacente causando vasodilatación. Los niveles plasmáticos de adrenomedulina están elevados en la hipertensión arterial, insuficiencia cardíaca, infarto de miocardio, insuficiencia renal, diabetes complicada, así como en el shock séptico. Los efectos biológicos de adrenomedulina, así como la demostración de niveles plasmáticos elevados del mismo en diversas patologías cardiovasculares y renales parecen confirmar su papel en la regulación de la presión arterial y del equilibrio hidroelectrolítico, aunque todavía son necesarios más estudios para dilucidar su papel fisiopatológico en las enfermedades cardiovasculares (AU)

Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.

BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.

[Autonomic dysfunction in chronic hypotension associated with uremia]. / Disfunción autonómica en la hipotensión crónica asociada a la uremia.

BACKGROUND: Chronic hypotension is a not uncommon complication among hemodialyzed patients which is responsible of an important morbidity. The autonomic nervous system (ANS) dysfunction seems to play a key role in the pathogenesis of chronic hypotension. METHODS: In order to study whether ANS dysfunction is responsible for chronic hypotension in hemodialyzed patients, the authors evaluated the integrity of the whole baroreflex arc by the Valsalva's manoeuver, of parasympathetic efferent pathway by the deep-breathing test and of sympathetic efferent pathway by the hand-grip test in 16 hemodialyzed patients with chronic hypotension, 17 normotensive hemodialyzed patients and 17 normal control subjects. Plasma catecholamine levels were also measured in these patients. RESULTS: In normotensive patients, Valsalva's manoeuver response (p < 0.005) and deep-breathing test response (p < 0.05) were lowered, while hand-grip test response was preserved. In chronic hypotensive patients, in addition to an impaired deep-breathing test (p < 0.05), a further reduced Valsalva's manoeuver response and a lower pressor response to hand-grip test were observed (p < 0.001). Catecholamine levels were higher in both groups of patients (p < 0.01) with respect to control subjects, specially in chronic hypotensive patients. CONCLUSIONS: In hemodialyzed patients (both normotensive and hypotensive) the whole baroreflex function and parasympathetic response are impaired. The lower pressor response to hand-grip test observed in hypotensive patients, in spite of the higher catecholamine levels, suggest that in these patients the cardiovascular dysfunction cannot be ascribed to a reduced sympathetic "outflow" but to a resistance of the target organs (heart and vessels) to the sympathetic stimulation.