Objective: To evaluate mechanisms of vasodilation in sepsis by comparing responses of resistance arterioles to vasopressin in rat cremaster muscle of septic and control rats.
Design: Prospective, experimental study.
Setting: Experimental animal laboratory.
Subjects: Twenty male rats, anesthetized with ketamine and acepromazine.
Interventions: Topical superfusion of vasoactive compounds on skeletal muscle resistance arterioles.
Measurements and main results: The effect of sepsis on responses to local application of vasopressin was investigated using in vivo videomicroscopy. Vasopressin was superfused topically on the cremaster muscle resistance arterioles (15 to 25 microns) of rats made septic by cecal ligation and puncture, and the responses were compared with the responses of controls that underwent sham ligation. Responses to topically suffused vasopressin were also assessed in septic and control rats, before and after superfusion of the muscle with the nitric oxide synthase inhibitor NG-methyl-L-arginine (NMA). Sepsis produced a decrease in the vasoconstrictive effects of vasopressin; the maximal response was lower, and the concentration-response curve was shifted to the right in septic rats (p < .05). Contractions at vasopressin concentrations of 0.01, 1, and 10 nM were 39%, 36%, and 40%, respectively, of sham controls. Superfusion of the muscle with NMA partially restored arteriolar responsiveness in the septic rats, significantly increasing the arteriolar constriction of the septic rats in response to vasopressin. This effect was reversed with superfusion of excess L-arginine (1 mM).
Conclusions: This study illustrates the reduced responsiveness of the resistance arterioles of septic rats in response to vasopressin in vivo, and the partial restoration of responsiveness by concurrent application of NMA. In previous studies using this model, we have shown similar results using norepinephrine and endothelin-1, as well as angiotensin II. These findings, and the findings of this study, suggest a generalized abnormality in responsiveness of resistance arterioles to endogenous vasoconstrictors in sepsis. Partial reversal of this abnormality with NMA supports an important role for nitric oxide in mediating abnormal vasopressor responsiveness in sepsis.