Aims To compare the haemodynamic responses of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) in the forearm vascular bed of healthy male volunteers, and to investigate the role of neutral endopeptidase (NEP) in the metabolism of ADM. Methods On two separate occasions, ADM (1±30 pmol min x1 ) and PAMP (100±3000 pmol min x1 ) were infused into the brachial artery of eight male subjects, and forearm blood¯ow (FBF) assessed using venous occlusion plethysmography. In a second study, eight male subjects received the same doses of ADM, co-infused with either the NEP inhibitor thiorphan (30 nmol min x1 ) or the control vasoconstrictor noradrenaline (120 pmol min x1 ), on separate occasions. Both studies were conducted in a double-blind, randomized manner. Results ADM and PAMP produced a dose-dependent increase in FBF (Pj0.002). Based on the dose producing a 50% increase in FBF, ADM was y60 times more potent than PAMP. Thiorphan and noradrenaline produced similar reductions in FBF of 14t4% (mean t s.e. mean) and 22t6%, respectively (P=0.4). However, the area under the dose±response curve was signi®cantly greater during co-infusion of ADM with thiorphan than with noradrenaline (P=0.028), as was the maximum increase in FBF ratio (2.1t1.0 vs 1.2t0.2; P= 0.030). Conclusions ADM and PAMP both produce a local dose-related vasodilatation in the human forearm, but PAMP is y60 times less potent than ADM. In addition, NEP inhibition potentiates the haemodynamic effects of ADM. These ®ndings suggest that PAMP may not play a role in the physiological regulation of blood¯ow. However, in pathophysiological conditions such as hypertension and heart failure, NEP inhibition may exert a bene®cial effect by increasing the biological activity of ADM.
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