Marked synergism between vasopressin and angiotensin II in a human isolated artery

Objective: To determine the direct contractile effects of angiotensin II (AII) and vasopressin (VP), and the effects of combinations of these agonists, in human isolated gastroepiploic arteries in vitro. Design: Laboratory and clinical investigation. Setting: University laboratory and hospital. Subjects: Ring segments were prepared from gastroepiploic arteries obtained from 57 patients undergoing gastrectomy. Blood samples were obtained from ten patients after severe hemorrhage and from five healthy volunteers. Interventions: Mechanical activity in the rings was assessed using a strain gauge. Plasma concentrations of AII and VP in the blood samples were measured using radioimmunoassay kits. Measurements and Main Results: Both AII (1 or 10 ng/mL) and VP (100 or 500 pg/mL) produced concentration-dependent contractions in the rings. However, whereas VP produced reproducible sustained contractions, the contractile responses induced by multiple applications of AII showed marked desensitization (i.e., tachyphylaxis). Indeed, by the sixth application of either 1 ng/mL AII or 10 ng/mL AII, the contractile responses were <20% of the initial (control) response. During applications of AII after the sixth, the co-application of a low concentration of VP (100 pg/mL) fully restored the contractile response to AII in a clearly more-than-additive fashion. Similarly, the tachyphylaxis seen on AII application alone did not occur with repeated applications of an AII+norepinephrine mixture. In patients who had experienced hemorrhage, there were marked elevations of both AII and VP plasma concentrations, with values as high as 2.2 ng/mL and 550 pg/mL, respectively. Conclusion: These results indicate that there is a powerful synergism between the contractile effects of low-dose VP and AII in this human isolated artery. Moreover, the elevations of plasma AII and VP levels during hemorrhage suggest that this synergism may be both physiologically and clinically important in optimizing vasoconstriction and maintaining blood pressure in such critical states.