Hemodynamic, hormone, and urinary effects of adrenomedullin infusion in essential hypertension

We examined the effects of the vasodilator peptide adrenomedullin (AM) infu sed intravenously into subjects with essential hypertension. Eight men 39 t o 58 years old with uncomplicated hypertension (147/96+/-5/3 mm Hg at basel ine) were studied in a placebo-controlled, crossover design. Each subject r eceived intravenous AM in a low and a high dose (2.9 and 5.8 pmol (.) kg(-1 ) (.) min(-1) for 2 hours each) or vehicle-control (Hemaccel) infusion in a random order on day 4 of a controlled metabolic diet (80 mmol/d Na+, 100 m mol/d K+). Plasma AM reached pathophysiological levels during infusion (18/-4 pmol/L in low dose, 34+/-9 pmol/L in high dose) with a concurrent rise in plasma cAMP (+8.4+/-1.2 pmol/L, P<0.05 compared with control). Compared with control, high-dose AM increased peak heart rate (+17.8+/-2.3 bpm, P<0. 01), lowered systolic (-24.6+/-0.9 mm Hg; P<0.01) and diastolic (-21.9+/-1. 4 mmHg; P<0.01) blood pressure, and increased cardiac output (+1.0+/-0.1 L/ min in low dose, +2.9+/-0.2 L/min in high dose; P<0.01 for both). Despite a rise in plasma renin activity during high dose (P<0.05), aldosterone level s did not alter. Plasma norepinephrine levels increased 1295+/-222 pmol/L ( P<0.001) and epinephrine increased 74+/-15 pmol/L (P<0.05) with high-dose A M compared with control. AM had no significant effect on urine volume and s odium excretion. Ln subjects with essential hypertension, the intravenous i nfusion of ARI to achieve pathophysiological levels produced significant fa lls in arterial pressure, increased heart rate and cardiac output, and stim ulated the sympathetic system and renin release without concurrent increase in aldosterone. Urinary parameters were unaltered. Although AM has potent hemodynamic and neurohumoral effects in subjects with essential hypertensio n, the threshold for urinary actions is set higher.