POTENT AND LONG-LASTING VASODILATORY EFFECTS OF ADRENOMEDULLIN IN HUMANS - COMPARISONS BETWEEN NORMAL SUBJECTS AND PATIENTS WITH CHRONIC HEART-FAILURE

Background Adrenomedullin (ADM) is a recently discovered hypotensive p eptide that has been isolated from human pheochromocytoma cells. Obser vations that ADM is produced from cardiovascular tissue and is found i n plasma suggest that it may be important in the regulation of regiona l vascular resistance. Methods and Results Limb vascular responses to ADM were examined in 10 healthy subjects and compared with those in 18 patients with chronic heart failure (CHF). The peptide increased fore arm blood flow (FBF) from 2.7+/-0.3 to 11.8+/-0.9 mL . min(-1). 100 mL (-1) in the control group and from 2.4+/-0.3 to 6.5+/-0.7 mL . min(-1) . 100 mL(-1) in the CHF group. The ADM-induced FBF increase was signif icantly impaired in the CHF group (P<.01). After cessation of the infu sion, an increased FBF level was sustained for >60 minutes in the cont rol group, whereas in the CHF group the response returned to the basel ine in <30 minutes. The ADM infusion increased forearm skin blood flow in both groups (P<.05), whereas the skin blood flow response was impa ired in the CHF group (P<.01). The role of nitric oxide in ADM-induced vasorelaxation was also studied in 11 healthy subjects and 6 patients with CHF. FBF and skin blood flow responses during ADM administration were significantly attenuated by N-G-monomethyl-L-arginine administra tion in healthy control subjects (P<.05), whereas both flow responses remained the same in the CHF group. Conclusions These observations dem onstrate that ADM exerts a potent and long-lasting vasodilatory effect on skeletal muscle arteries with involvement of nitric oxide-dependen t mechanisms in normal human peripheral vasculature and that these vas cular effects are significantly attenuated in patients with CHF, in pa rt because of impaired production of nitric oxide in the fore arm resi stance vessels.