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Rapid increase of mineralocorticoids after furosemide in low-renin essential hypertension: Evidence for 18-hydroxycorticosterone to be a better marker than aldosterone

Die Mineralocorticoidsekretion nach Furosemid ist bei Patienten mit low-renin Hypertonie gesteigert: 18-Hydroxycorticosteron reagiert dabei empfindlicher als Aldosteron

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Summary

The response of plasma renin activity (PRA), plasma aldosterone, 18-hydroxycorticoster-one (18-OH-B), 18-hydroxydeoxycorticosterone (18-OH-DOC) and corticosterone to furosemide were compared in 20 normal control subjects, 16 patients with normal-renin essential hypertension (NREH) and 12 patients with low-renin essential hypertension (LREH). Analyses were performed before medication, and 15 min (supine) and 120 min (active orthostasis) after IV administration of 40 mg furosemide. In normotensive subjects PRA increased 15 min after administration of furosemide from 0.8±0.4 ng AI/ml·h (SD) to 3.4±1.4 (P<0.01), plasma aldosterone from 109±28 pg/ml to 139±40 (P<0.01) and 18-OH-B from 199±90 to 279±85 (P<0.01). In patients with NREH, PRA increased significantly less (P<0.01) and no significant increase of plasma aldosterone or 18-OH-B was found. PRA of patients with LREH (0.2±0.1 ng AI/ml·h) remained practically unchanged 15 min after furosemide administration, but in contrast to NREH aldosterone increased from 111±37 to 160±66 (P<0.05) and 18-OH-B from 162±101 to 261±71 pg/ml (P<0.01). The relative increase of plasma 18-OH-B was significantly greater in patients with LREH than in patients with NREH. The plasma levels of aldosterone and 18-OH-B 120 min after furosemide administration were significantly higher in normotensive subjects than in either hypertensive group (P<0.01). Corticosterone and 18-OH-DOC levels were the same in all investigated groups and increased significantly (P<0.01) only at 120 min after furosemide administration combined with active orthostasis. In summary, our results support the concept that sensitivity of the mineralocorticoid-producing cells is enhanced in patients with LREH. Postfurosemide 18-OH-B seems to be a better marker of this phenomenon than aldosterone.

Zusammenfassung

Das Verhalten der Plasmareninaktivität (PRA), des Plasmaaldosterons, des 18-Hydroxycorticosterons (18-OH-B), des 18-Hydroxydeoxycorticosterons (18-OH-DOC) und des Corticosterons wurde nach Furosemid an 20 Normalpersonen, 16 Patienten mit normal-renin Hypertonie (NREH) und 12 Patienten mit low-renin Hypertonie (LREH) untersucht. Die Blutentnahmen erfolgten unmittelbar vor der Gabe von 40 mg Furosemid i.v. sowie 15 min (im Liegen) und 120 min (aktive Orthostase) danach. Die Normalpersonen zeigten 15 min nach Furosemid einen Anstieg der PRA von 0,8±0,4 ng AI/ml·min (SD) auf 3,4±1,4 (P<0,01), des Plasmaaldosterons von 109±28 pg/ml auf 139±40 (P<0,01) und des 18-OH-B von 199±90 pg/ml auf 279±85 (P<0,01). Bei Patienten mit NREH stieg die PRA signifikant geringer an (P<0,01). Dementsprechend wurde kein signifikanter Anstieg des Plasmaaldosterons und des 18-OH-B gefunden. Bei Patienten mit LREH blieb die PRA (basal 0,2±0,1) 15 min nach Furosemid praktisch unverändert. Das Plasmaaldosteron jedoch stieg von 111±37 auf 160±66 (P<0,05) und das 18-OH-B von 162±101 auf 261±71 an (P<0,01). Der relative Anstieg des 18-OH-B bei Patienten mit LREH war im Vergleich zu Patienten mit NREH signifikant höher. 120 min nach Furosemid lagen die Plasmaspiegel des Aldosterons und des 18-OH-B bei Normalpersonen signifikant höher als in den beiden Patientengruppen (P<0,01). Die Corticosteron und 18-OH-DOC Plasmaspiegel zeigten zwischen den untersuchten Gruppen kein differentes Verhalten, und es fand sich nur 120 min nach Furosemid in Kombination mit aktiver Orthostase ein signifikanter Anstieg. Die Ergebnisse zeigen, daß die Sekretion der Mineralcorticoide bei Patienten mit LREH unmittelbar nach Furosemid gesteigert ist, obwohl die PRA unverändert bleibt. 18-OH-B ist anscheinend für dieses Phänomen ein empfindlicherer Index als Aldosteron.

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Supported by Deutsche Forschungsgemeinschaft, grant Wi 548/1,2

Presented in part at the Kongress der Deutschen Gesellschaft für Innere Medizin, Wiesbaden, 1981

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Witzgall, H., Thayil, G. & Weber, P.C. Rapid increase of mineralocorticoids after furosemide in low-renin essential hypertension: Evidence for 18-hydroxycorticosterone to be a better marker than aldosterone. Klin Wochenschr 60, 847–852 (1982). https://doi.org/10.1007/BF01728351

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