Rates of Growth and of Remodelling as Factors in the Genesis of Vascular and Osseous Lesions of Odoratism in Rats

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Abstract
Evidence is presented in support of the view that lesions in vessels, bones, and perhaps in connective tissues generally, induced by feeding L. odoratus seeds to rats, may be attributable primarily to some disturbance in the neogenesis of fibres during the growth, regeneration, and/or repair of connective tissues. This failure seems to be at a stage after sulphation of those mucopolysaccharides which accumulate in connective tissue ground substance during fibre formation. It is suggested that the aortic ruptures may be the result of some derangement in the balance between lysis and regeneration of elastic membranes, which probably occur simultaneously during the normal growth and remodelling of the aorta. This interpretation differs from that provided by other workers who attribute aortic ruptures solely to elastolysis. Evidence from the study of lesions in bones and alterations in repair processes around the aorta in L. odoratus-fed adult and weanling rats supports the interpretations here presented. The frequency of ‘double-shafts’ as well as other deformities of long bones are taken as clear indications of disorganized remodelling of bones during growth. These studies of the aortic reactions in rats fed L. odoratus seeds also substantiate our previous contention that the integrity of the collagen-like ‘cores’ of the VEM’s is probably intimately dependent upon their ‘sleeves’ of reticulin and polysaccharides. The association of damage to the elastic membranes with distinct alterations in the reticulin and mucopolysaccharide contents immediately around and also between aortic VEM’s confirm our previous findings in this regard. There are indications, too, from histochemically detectable increases in circulating mucopolysaccharides, from the marked increases in osseous mast-cells and from reported delay in blood-clotting, that widespread disturbances in polysaccharide metabolism prevail in odoratus-intoxicated rats. Some possible implications of these findings for understanding the genesis of human arterial lesions are briefly discussed with special reference to a developmental approach to the aetiology and pathogenesis of these vascular reactions in terms of general features of connective tissue regeneration and repair.