Microvascular endothelial cell control of peripheral vascular resistance during sepsis

Objective: To determine the endothelial-dependent control of decreased peri pheral vascular resistance in skeletal muscle microvessels during evolving sepsis. Materials and Interventions: Acute (4 hours, n = 7), established (24 hours, n = 7), or chronic (72 hours, n = 8) infection was induced in Sprague-Dawl ey rats (150-175 g) by injecting Escherichia coli and Bacteroides fragilis (1 x 10(9) colony-forming units for both) into a subcutaneous sponge. Contr ol animals were injected with an isotonic sodium chloride solution and anal yzed 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 p recapillary fourth-order (A4) arterioles in cremaster muscle in vivo with v ideomicroscopy. Acetylcholine dose-response curves were used to determine V ascular reactivity by calculating the concentration of ACH necessary to eli cit 50% of the maximal dilator response. Main Outcome Measures: In vivo reactivity of striated muscle microvessels t o the dilation agonist ACH during acute, established, and chronic infection . Results: A1 vessels were unresponsive to all doses of ACH at all time point s. A4 vessels showed an increased dilator response during short-term treatm ent, which deteriorated over time to depressed dilation during chronic infe ction. Conclusions: Precapillary A4 vessels have increased dilator reactivity duri ng early sepsis, which progresses to depressed levels with chronic infectio n. A1 microvessels remain dilated and are not substantially influenced by e ndothelial, dilator mechanisms initiated by AGH. Maximum dilation of the la rge A1 vessels appears to contribute to the decrease in peripheral vascular resistance noted during systemic infection.