RESUMEN
Animals and humans undergoing treatment with ciclosporin (CS) show a reversible increase in renal vascular resistance and a decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. We evaluated the effects of a 1-week treatment with CS on creatinine clearance, renal arachidonic acid metabolites, plasma renin activity (PRA), plasma aldosterone levels, urinary excretion and plasma levels of catecholamines in 7 patients with idiopathic uveitis. We show that CS treatment induces a significant (p less than 0.05) decrease in creatinine clearance (from 132 +/- 0.5 to 108 +/- 8 ml/min); urinary 6-keto-PGF1 excretion (from 17.8 +/- 4.9 to 10.9 +/- 3.3 ng/mmol creatinine), urinary thromboxane B2 excretion (from 7.0 +/- 1.0 to 3.6 +/- 0.9 ng/mmol creatinine), upright PRA (from 4.2 +/- 0.9 to 2.3 +/- 0.8) and supine PRA (from 2.0 +/- 0.5 to 1.1 +/- 0.3). We found no change in plasma aldosterone levels and plasma levels and urinary excretion of catecholamines. We suggest that the reversible renal vasoconstriction observed in patients treated with CS may be induced by inhibition of renal prostacyclin synthesis. In this setting inhibition of PRA and angiotensin II formation may impair autoregulation of effective filtration pressure and therefore glomerular filtration rate.
Asunto(s)
Catecolaminas/sangre , Ciclosporinas/farmacología , Riñón/metabolismo , Prostaglandinas/sangre , Renina/sangre , Uveítis/sangre , Adulto , Anciano , Ciclosporinas/uso terapéutico , Epoprostenol/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prostaglandinas/orina , Tromboxano B2/orina , Uveítis/tratamiento farmacológicoRESUMEN
Tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) activities, dopamine (DA), noradrenaline (NA), adrenaline (A), met 5-enkephalin (Met-Enk), leu5-enkephalin (Leu-Enk), dynorphin (Dyn) and beta-endorphin (beta-end) were measured simultaneously in ten human pheochromocytomas = 1 - TH activity was highly variable, from 22 to 2220 U/g tissue. 2 - DBH activity, in contrast, was rather constant, from 96 to 582 U/g. 3 - Catecholamines (A and NA) concentrations showed only small variations. 4 - The four opioid peptides were detected in all cases and exhibited a wide range of tissue concentrations (Enk much greater than Dyn greater than beta-end). 5 - Met-Enk and Leu-Enk concentrations were highly correlated; no correlation was observed with the other opioid peptides. 6 - A very strong correlation was observed between enkephalins concentrations and both catecholamines concentrations and DBH activities. These results are discussed in term of the significance of the co-localization of these various biologically active substances, principally with regard to the possible regulation of catecholamine synthesis by opioid peptides and conversely.