Effect of hydralazine and dihydralazine on connective tissue and binding to serum protein

Hydralazine and dihydralazine, chelators of Fe2+, Fe3+ and Mn2+ ions, inhibited collagen biosynthesis in organ culture of chicken embryo tibiae. Both substances inhibited the in vitro hydroxylation of [14C]Pro-labelled protocollagen by protocollagen proline hydroxylase. A decreased incorporation of [14C]-D-glucosamine into glyco- and/or muco-proteins was found under the effect of the two drugs. Dihydralazine, a cationic compound, was bound to DNA and acid mucopolysaccharides (glycosaminoglycans), forming an insoluble complex. Both substances were bound to serum alpha 2-globulin. Subcutaneous injections of dihydralazine in rats produced a local as well as a general toxic effect.