Regulation of activity of serine proteinase inhibitor a1-antitrypsin and nonspecific proteinase inhibitor alpha(2)-macroglobulin in the blood by nitric oxide was studied in intact rats and animals with damage to capsaicin-sensitive nerves. Nonselective nitric oxide synthase inhibitor L-NAME produced a dose-dependent increase in alpha(1)-antitrypsin activity in intact animals. Neuronal NO synthase inhibitor 7-nitroindazole increased alpha(2)-macroglobulin activity. Deafferentation with capsaicin was followed by a decrease in alpha(1)-antitrypsin activity. Both inhibitors of nitric oxide synthase increased activity of alpha(1)-antitrypsin in capsaicin-receiving rats. Nitric oxide precursor L-arginine had a normalizing effect on reduced activity of alpha(1)-antitrypsin after capsaicin deafferentation. Our results suggest that nitric oxide has a modulatory effect on activity of proteinase inhibitors and is involved in the effector influence of capsaicin-sensitive nerves on alpha(1)-antitrypsin activity.