Aortic histamine synthesis and aortic albumin accumulation in diabetes: activity-uptake relationships.
The relationship between inhibition of aortic histamine synthesis induced by varied dosages of alpha-hydrazinohistidine (alpha HH) and aortic uptake of fluorescein-labeled bovine serum albumin (FITCBSA) was examined in 40 male Wistar rats made diabetic by streptozotocin. Compared to nondiabetic animals, aortic uptake of FITCBSA in untreated diabetic animals was increased 43%. alpha HH administration produced essentially a complete inhibition of this accelerated histamine synthesis in diabetic animals at all dosages examined and likewise prevented an increase in aortic FITCBSA uptake among these animals. In diabetic animals, aortic histamine synthesis and aortic FITCBSA uptake showed a significant, strong positive correlation (r = 0.822, P less than 0.001) when examined in relation to the degree of inhibition of accelerated aortic histamine synthesis achieved among the individual animals. These data support the hypothesis that elevations in de novo aortic histamine formation, and thus elevations in the inducible histamine pool, are responsible, at least in part, for increased aortic uptake of macromolecules in diabetes. Since increases in various permeability characteristics occur early in atherogenesis, these data also indicate that expansion of the nascent histamine pool occurring in diabetes may be an important factor in the predisposition of diabetics to atherosclerotic vascular disease.
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins / Q000378:metabolism*; D006632:Histamine / Q000096:biosynthesis*; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006639:Histidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000378:metabolism*
D005452:Fluoresceins; D006633:Histamine Antagonists; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; C045518:alpha-hydrazinohistidine; D006639:Histidine; D006632:Histamine; D006640:Histidine Decarboxylase; D016650:Fluorescein-5-isothiocyanate