Microvascular endothelial cell control of peripheral vascular resistance during sepsis.
OBJECTIVE
To determine the endothelial-dependent control of decreased peripheral vascular resistance in skeletal muscle microvessels during evolving sepsis.


METHODS
Acute (4 hours, n=7), established (24 hours, n=7), or chronic (72 hours, n=8) infection was induced in Sprague-Dawley rats (150-175 g) by injecting Escherichia coli and Bacteroides fragilis (1 x 10(9) colony-forming units for both) into a subcutaneous sponge. Control animals were injected with an isotonic sodium chloride solution and analyzed at the same time points: (n=6-8 per group). Dilation in response to the topically applied endothelial-dependent agonist acetylcholine (ACH) (1 x 10(-9) to 1 x 10(-5) mol/L) was measured in inflow first-order (A1) and precapillary fourth-order (A4) arterioles in cremaster muscle in vivo with videomicroscopy. Acetylcholine dose-response curves were used to determine vascular reactivity by calculating the concentration of ACH necessary to elicit 50% of the maximal dilator response.


METHODS
In vivo reactivity of striated muscle microvessels to the dilation agonist ACH during acute, established, and chronic infection.


RESULTS
A1 vessels were unresponsive to all doses of ACH at all time points. A4 vessels showed an increased dilator response during short-term treatment, which deteriorated over time to depressed dilation during chronic infection.


CONCLUSIONS
Precapillary A4 vessels have increased dilator reactivity during early sepsis, which progresses to depressed levels with chronic infection. A1 microvessels remain dilated and are not substantially influenced by endothelial dilator mechanisms initiated by ACH. Maximum dilation of the large A1 vessels appears to contribute to the decrease in peripheral vascular resistance noted during systemic infection.
Tucker
J J
JJ
Department of Physiology, University of Louisville School of Medicine, KY 40292, USA.
Wilson
M A
MA
Wead
W B
WB
Garrison
R N
RN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014699:Venules / Q000187:drug effects / Q000503:physiopathology
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine