Relationship between inhibition of aortic histamine formation, aortic albumin permeability and atherosclerosis.

Effects of partial inhibition of aortic histamine formation on aortic albumin uptake and lipid deposition were examined in male, New Zealand white rabbits maintained on Purina Rabbit Chow containing 0.5% cholesterol for a 2-week period. Aortic histamine synthesis was inhibited by partial inhibition of aortic histidine decarboxylase (HD) through administration of alpha-hydrazinohistidine (alpha-HH, MK785, Regis Chemical Co., 25 mg/kg, i.p. at 12-h intervals). Additional rabbits were maintained on either the cholesterol diet or on Purina Rabbit Chow without cholesterol. Results indicate that administration of alpha-HH for the 2-week period produced a 31% reduction (P less than 0.05) in aortic HD activity in those rabbits maintained on the cholesterol diet, and that concurrently there was a 51% reduction in aorta albumin uptake (P less than 0.025) and a 63% reduction in the extent of oil red O staining. By regression analysis a significant correlation coefficient (r = 0.71, P less than 0.005) was obtained between the aortic albumin uptake and the aortic histamine forming capacity (HFC) in rabbits maintained on this cholesterol diet. These findings indicate that the aortic HD system may be an important enzymatic coupler involved in vascular permeability alterations occurring early in the atherogenic sequence.