IMPAIRED MICROVASCULAR VASOCONSTRICTIVE RESPONSES TO VASOPRESSIN IN SEPTIC RATS

Objective: To evaluate mechanisms of vasodilation in sepsis by compari ng responses of resistance arterioles to vasopressin in rat cremaster muscle of septic and control rats. Design: Prospective, experimental s tudy. Setting: Experimental animal laboratory. Subjects: Twenty male r ats, anesthetized with ketamine and acepromazine. Interventions: Topic al superfusion of vasoactive compounds on skeletal muscle resistance a rterioles. Measurements and Main Results: The effect of sepsis on resp onses to local application of vasopressin was investigated using in vi vo videomicroscopy. Vasopressin was superfused topically on the cremas ter muscle resistance arterioles (15 to 25 pm) 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 topic ally suffused vasopressin were also assessed in septic and control rat s, before and after superfusion of the muscle with the nitric oxide sy nthase inhibitor N-G-methyl-L-arginine (NMA). Sepsis produced a decrea se in the vasoconstrictive effects of vasopressin; the maximal respons e was lower, and the concentration-response curve was shifted to the r ight in septic rats (p < .05). Contractions at vasopressin concentrati ons of 0.01, 1, and 10 nM were 39%, 36%, and 40%, respectively, of sha m controls. superfusion of the muscle with NMA partially restored arte riolar 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 t he resistance arterioles of septic rats in response to vasopressin in vivo, and the partial restoration of responsiveness by concurrent appl ication of NMA. In previous studies using this model, we have shown si milar results using norepinephrine and endothelin-1, as well as angiot ensin II. These findings, and the findings of this study, suggest a ge neralized abnormality in responsiveness of resistance arterioles to en dogenous vasoconstrictors in sepsis. Partial reversal of this abnormal ity with NMA supports an important role for nitric oxide in mediating abnormal vasopressor responsiveness in sepsis.