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REDUCED Ca2+‐SENSITIVITY IN MESENTERIC RESISTANCE ARTERIES OF MICE WITH LPS‐INDUCED INFLAMATION
Author(s) -
Aytekin Betul,
Hunter Larry W.,
Sieck Gary C.,
Ouellette Yves
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb13-b
Subject(s) - phenylephrine , vasoconstriction , mesenteric arteries , medicine , endocrinology , chemistry , agonist , ec50 , stimulation , vascular resistance , vasodilation , in vitro , hemodynamics , receptor , artery , blood pressure , biochemistry
Two hallmarks of sepsis are decreased vascular resistance and hyporeactivity to vasoconstrictor agents. The aim of this study was to determine if these factors were reflective of reduced Ca 2+ ‐sensitivity in murine small mesenteric resistance arteries (MA). We used 4 th ‐order MA segments (~200 μm diameter) from mice injected with E. coli LPS (15 mg/kg i.p. 18 hr), an accepted model for sepsis, and compared reactivity with arteries from sham controls (vehicle). Endothelium‐intact (ACh‐responsive) MA segments were loaded with fura‐2 AM, pressurized at 60 mm Hg, and superfused in vitro with MOPS buffer at 37°C. MA diameter and global [Ca 2+ ] i were measured concurrently using light microscopy and a photomultiplier system. Concentration‐response curves to phenylephrine (PE, 10 −9 –10 −4 M), an α 1 ‐adrenoceptor agonist were conducted. PE‐induced vasoconstriction was reduced in LPS‐treated mice: the EC 50 was increased (2.07±0.45 μM vs 0.56±0.15 μM in shams) whereas the E max was reduced (19.26 ±4.35 % initial diameter vs 37.89±1.05 % in shams). However, concurrent [Ca 2+ ] i levels at each PE concentration (as indicated by incremental increases in the fura‐2 340/380 emission ratio) were unaffected in LPS‐treated mice compared to shams, consistent with reduced Ca 2+ ‐sensitivity ( figure). We conclude that LPS‐induced vascular inflammation results in reduced Ca 2+ –σενσιτιϖιτψ το α 1 ‐adrenoceptor stimulation in murine MA.Supported by the Mayo Foundation.