Nitric oxide protects venules against histamine-induced leaks

Objective: The goal of the present study was to investigate the prophylactic role of nitric oxide (NO) in the mesenteric microvasculature in preventing microvascular leakage subsequent to histamine application, and to evaluate the response of mast cells during these conditions. Methods: Regions of the rat mesenteric microcirculation were flushed free of blood and pretreated with either the nitric oxide donor sodium nitroprusside (SNP 10(-6) M) or Hepes-buffered saline containing 0.5% bovine serum albumin (HBS-BSA) for 15 minutes, then exposed to histamine (10(-3) M) for another three minutes. Ln another set of experiments, the microvasculature was treated with either histamine (10(-3) M) for three minutes or SNP (10(-6) M) for 15 minutes. A control group was treated with HBS-BSA for 15 minutes. Results: The protective role of NO was evaluated by its ability to reduce or prevent histamine-induced venular leaks. Mesenteric microvessels pretreated with SNP before histamine suffusion showed a significant decrease in both area and number of venular leaks following the perfusion of fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA). Although SNP pretreatment did not reduce the percentage of mast cells that degranulated in the presence of histamine, it did somewhat reduce the severity of the degranulation. Conclusion: This study demonstrated that nitric oxide availability protects mes enteric venules against histamine-induced leaks, but does not prevent degranulation of mast cells. Therefore, nitric oxide probably acts directly on venular endothelial cells to prevent leak formation.