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

Figures

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  Fig. 1. Outline of experimental protocol. Following incubation for 16-20 h with Captopril (10–2), Ang 1–7 (10–9), or vehicle, human microvessels were cannulated followed by two equilibration periods (30 mmHg and 60 mmHg, respectively). The Mas receptor antagonist A779 (10–5) was added during the second equilibration period. Following equilibration, vessels were exposed to propofol for 10 min prior to a phenylephrine (PE) dose–response curve (DRC) to assess vascular reactivity

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  Fig. 2. Efficacy of phenylephrine (PE) as a vasoconstrictor in human resistance arterioles. A significant (p < 0.05) reduction in PE-induced constriction was observed at 10–5 M in vessels treated with propofol alone (10–6 M; panel A). Pretreatment with captopril alone (10–2 M; panel B) did not affect alter the response to PE, but PE-induced vasoconstriction was significantly reduced in vessels treated with both captopril and propofol

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  Fig. 3. Role of the Mas receptor in phenylephrine resistance in captopril pretreated arterioles exposed to propofol. The Mas receptor antagonist A779 (10–5 M) alone did not affect PE-induced vasoconstriction versus control (panel A). Addition of A779 before propofol restored the ability of PE to constrict arterioles pretreated with captopril (panel B). Ang 1–7 alone (10–9 M) did not affect PE-induced constriction (panel C). PE-induced vasoconstriction of arterioles pretreated with Ang 1–7 was significantly (P < 0.05) attenuated compared with those exposed to propofol alone (panel D). However, A779 partially restored the vasoconstrictive effect of PE in microvessels pretreated with Ang 1–7 during propofol exposure to propofol

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  Fig. 4. Schematic illustration representing alternative metabolism of angiotensin I and the role of the Mas receptor in attenuation of phenylephrine-induced vasoconstriction during ACE inhibition in the presence of propofol. Abbreviations: ACE1 = angiotensin converting enzyme 1; ACE2 = angiotensin converting enzyme 2; PEP = prolyl-endopeptidase; NEP = neutral endopeptidase; AT1 = angiotensin receptor 1