Vasoactive effects of adrenotensin and its interactions with adrenomedullin

Objective To investigate the vasoactive effects of adrenotensin and the interactions between adrenotensin and adrenomedullin (ADM). Methods Isolated rat aortic tension, rat mean arterial pressure and (3)H-TdR incorporation of rat vascular smooth muscle cells were measured. Isolated rat aortas were incubated in K-H solution containing adrenomedullin or adrenotensin. The released adrenotensin or adrenomedullin (in incubation medium) from rat aortas was measured by radioimmunoassay. Results 1×10(-8)and 1×10(-7)mol/L adrenotensin augmented rat aortic tension in a dose-dependent manner (P<0.01). An intravenous bolus injection of adrenotensin (2.5 nmol/kg, iv) increased the mean arterial pressure by 28% in anesthetized rats (P<0.01). 1×10(-7)mol/L adrenotensin increased (3)H-TdR incorporation in cultured rat vascular smooth muscle cells by 55% (P<0.01). Adrenomedullin inhibited these activities of adrenotensin to different extents. 1×10(-9), 1×10(-8)and 1×10(-7)mol/L adrenotensin decreased adrenomedullin release rates by 19%, 35% and 46%, respectively (P<0.05 or P<0.01) and 1×10(-8)mol/L adrenomedullin also inhibited adrenotensin release by 45% from rat aorta (P<0.01).Conclusion Adrenotensin is a novel peptide that elicits the activities of vasoconstriction, pressor effects and induces the proliferation of vascular smooth muscle cells. There is antagonism in vascular activities and reciprocal inhibition in the release between adrenotensin and adrenomedullin. These interactions are manifestations of intramolecular regulation of proadrenomedullin (Pro-ADM).