Hypotensive effect of a newly identified peptide, proadrenomedullin N-terminal 20 peptide

Abstract

Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are both derived from proadrenomedullin, exhibit marked hypotensive effects. We recently reported that PAMP but not AM reduced the release of norepinephrine from peripheral sympathetic nerve endings. Our present objective was to clarify the involvement of the sympathetic nervous system in the hypotensive action of PAMP and AM. Intravenous administration of PAMP (10, 20, and 50 nmol/kg) to conscious rats induced less reflex tachycardia (5 +/- 5, 10 +/- 5, and 14 +/- 6 beats per minute [bpm]) than that of AM in 0.1, 0.5, and 1.0 nmol/kg doses (5 +/- 8, 20 +/- 7, and 38 +/- 5 bpm, P < .01) although both agents showed similar hypotensive effects. We evaluated the effect of PAMP on blood pressure in pithed rats whose sympathetic nervous systems were abolished. In pithed rats, AM (-2 +/- 1, -7 +/- 1, and -10 +/- 3 mm Hg; NS, P < .05, and P < .01, respectively) but not PAMP evoked hypotension. In contrast, administration of PAMP (-3 +/- 1, -11 +/- 2, and -14 +/- 4 mm Hg; P < .05, P < .01, and P < .01, respectively) as well as adrenomedullin (-2 +/- 2, -10 + 3, and -15 +/- 4 mm Hg; NS, P < .01, and P < .01) significantly reduced blood pressure in electrically stimulated, pithed rats, which had reached almost the same levels as in conscious rats. In electrically stimulated, pithed rats, plasma norepinephrine level was reduced by PAMP but not by vehicle or AM. These findings suggest that the hypotensive effect of PAMP is mainly due to inhibition of peripheral sympathetic nerve activity.