Hypotensive and natriuretic actions of adrenomedullin in subjects with chronic renal impairment

Plasma levels of adrenomedullin are increased in chronic renal failure. The significance of this finding is uncertain, because the biological effects of adrenomedullin in renal impairment are unknown. Therefore, we studied th e effects of adrenomedullin infusion in subjects with chronic renal impairm ent. Eight males with IgA nephropathy and plasma creatinine of 0.19 +/-0.03 mmol/L (mean +/- SEM) were studied in a vehicle-controlled crossover desig n, Each subject was studied twice; subjects were administered either adreno medullin at a low dose and then a high dose (2.9 and 5.8 pmol/kg per minute , respectively, for 2 hours each) or a 4-hour vehicle control (Hemaccel), i n random order, on day 4 of controlled metabolic diets. Adrenomedullin infu sion achieved plasma adrenomedullin concentrations in the pathophysiologica l range after the low (31.2 +/-5.1 pmol/L) and high (47.4 +/-4.3 pmol/L) do se, and plasma cAMP was increased. Compared with vehicle control, high-dose adrenomedullin increased peak heart rate (+21.7 +/-3.3 bpm, P<0.01) and ca rdiac output (+2.9<plus/minus>0.2 L/min, P<0.01) and lowered both systolic and diastolic blood pressures by >10 mm Hg (P<0.05), Plasma renin activity, angiotensin II, and norepinephrine increased by up to 50% above baseline l evels (P<0.05 for all), whereas aldosterone and epinephrine were unchanged. Urinary volume and sodium excretion increased significantly (P<0.05) with low-dose adrenomedullin, whereas creatinine clearance was stable, and prote inuria tended to decrease. In subjects with chronic renal impairment due to IgA nephropathy, adrenomedullin infusion lowered blood pressure, stimulate d sympathetic activity and renin release, and caused diuresis and natriures is. Adrenomedullin may have a role in modulating blood pressure and kidney function in renal disease.