Vasoactive effects of adrenotensin and its interactions with adrenomedullin

Objective To investigate the vasoactive effects of adrenotensin and the int eractions between adrenotensin and adrenomedullin (ADM). Methods isolated rat aortic tension, rat mean arterial pressure and H-3-TdR incorporation of rat vascular smooth muscle cells were measured. Isolated rat aortas were incubated in K-H solution containing adrenomedullin or adre notensin. The released adrenotensin or adrenomedullin tin incubation medium ) from rat aortas was measured by radioimmunoassay. Results 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin augmented rat aortic t ension in a dose-dependent manner (P < 0.01). An intravenous bolus injectio n of adrenotensin (2.5 nmol/kg, iv) increased the mean arterial pressure by 28% in anesthetized rats (P < 0.01). 1 x 10(-7)mol/L adrenotensin increase d 3H-TdR incorporation in cultured rat vascular smooth muscle cells by 55% (P < 0.01). Adrenomedullin inhibited these activities of adrenotensin to di fferent extents. 1 x 10(-9), 1 x 10(-8) and 1 x 10(-7) mol/L adrenotensin d ecreased adrenomedullin release rates by 19%, 35% and 46%, respectively (P < 0.05 or P < 0.01) and 1 x 10(-8)mol/L adrenomedullin also inhibited adren otensin release by 45% from rat aorta ( P < 0.01). Conclusion Adrenotensin is a novel peptide that elicits the activities of v asoconstriction, presser effects and induces the proliferation of vascular smooth muscle cells. There is antagonism in vascular activities and recipro cal inhibition in the release between adrenotensin and adrenomedullin. Thes e interactions are manifestations of intramolecular regulation of proadreno medullin (Pro-ADM).