Angiopoietin-1 increases arteriolar vasoconstriction to phenylephrine during sepsis

Sepsis leads to a reduction in vascular tone and a loss of vasoconstriction in response to catecholamines. We propose that angiopoietin-1 (Ang-1), which is known to modulate vascular inflammation and nitric oxide (NO), could improve responsiveness to vasopressor agents during sepsis. Mesenteric arterioles (300-400 μm) from rats (n = 19) were mounted in a pressurized myograph and incubated with lipopolysaccharide (LPS, 50 μg/mL) for up to 4 h to model sepsis. Vasoconstriction (mean ± SD) to phenylephrine (10− 8-10− 3 M) was reduced in the presence of LPS (4 h, pD2: 5.8 ± 0.2 (controls, n = 6), 1.4 ± 2.2 (LPS, n = 6); maximal constriction: 48.2 ± 4.8% (controls), 2.6 ± 5.8% (LPS), P < 0.05). However, in the presence of Ang-1 (250 ng/mL) phenylephrine caused greater vasoconstriction compared to LPS alone (4 h, pD2: 4.5 ± 2.1; maximal constriction: 12.6 ± 4.0% (n = 7), P < 0.05). In conclusion, Ang-1 increases vasoconstriction to phenylephrine in the presence of LPS. During sepsis therefore, Ang-1 increases vascular reactivity and has the potential to increase blood pressure and decrease vasopressor requirements in vivo.