Renal Effects of Adrenomedullin in the Rat

Abstract

Abstract

We investigated the effects of a constant infusion of adrenomedullin (ADM) on renal hemodynamics and fluid electrolyte excretion in the rat. Following baseline measurements, eight rats received an intravenous infusion of 5 μg of rat ADM (167 ng/min) for 30 min at 10 μl/min. Eight additional rats received 0.9% saline at 10 μl/min instead of ADM. Renal function was measured during this period and for two consecutive 20-min periods following termination of the ADM or vehicle infusion. Mean arterial pressure decreased from a baseline of 113±3 to 102±1 mm Hg at 25 min of ADM infusion and returned towards control after the ADM infusion was terminated. This modest hypotensive effect was associated with an increase in heart rate from 366±10 to 384±9 bpm, which continued to remain elevated after the ADM infusion was stopped. Urinary sodium excretion increased from 348±57 to 813±172 nEq/min during ADM infusion and continued to increase to 1141±347 nEq/min after the infusion of ADM was terminated. Urinary potassium excretion increased from 1.94±0.22 to 2.75±0.24 μl/min during ADM infusion. Urine flow tended to increase (P = 0.08) from 7.0±0.5 to 8.1±0.6 μl/min during ADM infusion and continued to increase to 9.7±1.5 μl/min after the infusion was stopped. Renal plasma flow increased from 3.22±0.22 to 3.82±0.20 ml/min/g kidney wt during ADM infusion and continued to increase to 4.14±0.22 ml/min/g kidney wt after the ADM infusion was stopped. Glomerular filtration rate averaged 1.11±0.07 ml/min/g kidney wt during baseline and did not significantly change during or after ADM infusion. These results indicate that a constant infusion of adrenomedullin, at a dose that results in a minimal hypotensive effect increases renal plasma flow and urinary sodium excretion in the rat.