title: Angiopoietin-1 increases arteriolar vasoconstriction to phenylephrine during sepsis.
abstract: 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 microm) from rats (n=19) were mounted in a pressurized myograph and incubated with lipopolysaccharide (LPS, 50 microg/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.
authors: University of Sheffield, Academic Anaesthesia Unit, Microcirculation Research Group, K Floor, Royal Hallamshire Hospital, Sheffield, UK.
authors: Emma
authors: E
authors: Hall
authors: Zoë Ls
authors: ZL
authors: Brookes
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000098:blood supply; D010656:Phenylephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D042683:Angiopoietin-1; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D010656:Phenylephrine