Blockade of endothelial Mas receptor restores the vasomotor response to phenylephrine in human resistance arterioles pretreated with captopril and exposed to propofol

Abstract

Abstract Background Hypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1–7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril. Methods The internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10–9 to 10–5 M) in the presence and absence of propofol (10–6 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10–5 M; added 30 min before phenylephrine) in separate experimental groups. Additional groups of arterioles were incubated for 16 to 20 h with captopril (10–2 M) or Ang 1–7 (10–9 M) before experimentation with phenylephrine, propofol, and A779. Results Propofol blunted phenylephrine-induced vasoconstriction in normal vessels. Captopril pretreatment alone did not affect vasoconstriction, but the addition of propofol markedly attenuated the vasomotor response to phenylephrine. A779 alone did not affect vasoconstriction in normal vessels, but it restored vasoreactivity in arterioles pretreated with captopril and exposed to propofol. Ang 1–7 reduced the vasoconstriction in response to phenylephrine. Addition of propofol to Ang 1–7-pretreated vessels further depressed phenylephrine-induced vasoconstriction to an equivalent degree as the combination of captopril and propofol, but A779 partially reversed this effect. Conclusions Mas receptor activation by Ang 1–7 contributes to phenylephrine-resistant vasodilation in resistance arterioles pretreated with captopril and exposed to propofol. These data suggest an alternative mechanism by which refractory hypotension may occur in anesthetized patients treated with ACE inhibitors.

Keywords

• Angiotensin converting enzyme inhibitor
• Ang 1–7
• Mas receptor
• Propofol
• Vasodilation
• Resistance arterioles