Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta

The effects of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenotensin (ADT) on adrenomedullin (ADM)-induced vasodilation were investigated in aortic rings from rat. ADM (10(-9) to 10(-7)M) relaxed the aorta preconstricted with phenylephrine in a concentration-dependent manner. Denudation of endothelium or pretreatment with nitric oxide synthase (NOS) inhibitor, L-NAME, attenuated the vasodilatory action of ADM. ADM-induced vasorelaxation in the aortic rings with endothelium was converted to contraction by PAMP, but not by ADT. The ADM-induced vasodilation was not affected by PAMP in aorta rings without endothelium or in intact aortic rings pretreated with L-NAME. ADM-stimulated nitrite production and NOS activity of the aortas, which was inhibited by PAMP, ADT or PAMP plus ADT. ADM, PAMP, and ADT increased the cyclic adenosine monophosphate (cAMP) contents in vascular tissue. The combination of ADM with PAMP or ADT caused a smaller increase in cAMP level as compared with that of PAMP or ADT alone. These results show that ADM-induced endothelium-dependent vasodilation could be converted to vasoconstriction in the presence of PAMP, probably through a NO-dependent pathway. There was no indication that cAMP was involved in the converting effect of PAMP on ADM vasodilator action.