Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry and Computational Chemistry

Abstract

Morphological and Neurochemical Plasticity of the Carotid Body after Long-Term Hypoxia: Vascular and Cellular Involvement, Morphometric Study in Meriones shawi Rats

Author(s): Abdenbi Schamel, Abdellatif Chaouti, Mountasser Douma and Brahim Sabour

Morphological changes in carotid body (CB) were studied in Meriones shawi rats that were made hypoxic by placing them in poor area inspired oxygen (10 % O2, 28 days) in a normobarique room. The comparisons were carried out with animals kept in normoxia. At the end of the experimental period, hypertrophy CB was observed in all hypoxic animals. It induced an increase in the size of the organ by a factor of 3.8. In an attempt to elucidate the mechanisms involved in this phenomenon, a quantitative study was performed on serial 5-μm thick sections. The morphometric results concern the extravascular compartment (connective tissue islets of glomus cells) and the vascular compartment.1) The extravascular surface (by section) has increased by +67.5 % and the extravascular underwent an increase of +88 %. However, when the extravascular volume is expressed relative to the volume of CB no significant change was observed. 2) The volume density (Dv) of the islets of glomus cells underwent a slight but non-significant decrease of -7.4%, while the Dv of connective tissue has undergone a significant increase of +50.8%. These results demonstrate that increase observed in the extravascular space of hypoxic CB was not due to cell multiplication, as no mitotic figures were observed. It took place by hypertrophy of type I cells and by an increase in the size of the interstitial space. 3) Regarding the vascular compartment, the Dv of microvessels has increased +99.6%, total vascular volume increased by +398% while the volume of the small vessels (<12 microns in diameter) showed only a slight increase of +44.1%. These same parameters when expressed relative to the volume of CB show that the total vascular volume has underwent a slight increase of +32% and that the volume of small vessels has decreased by 619 %. Finally, the variation in the CH of the number density of the small vessels and the change in the surface of the endothelial lining of small and large vessels (> 12 mm in diameter) show that the observed increase in the total vascular volume would largely due to increased volume of large vessels. 4) A high number of type I cells that react to the chromaffin reaction was detected in hypoxic animals. Data show that the number of positive type I cells in this reaction was increased by 80.8-times. Their Dv was enhanced by 32-times. In the absence of cell multiplication signs, these results suggest that CH induced the appearance of noradrenaline in glomus cells. All data obtained in Meriones shawi rats suggests that CB hypertrophy is due to an increase in total vascular volume primarily generated by large vessels and an increase in the extravascular volume. Glomus cells react to the CH by hypertrophy and increased, after a delay, of its noradrenaline content. This could be correlated to subsequent increase in the CB sensitivity. We suggest that ventilatory adaptation related to carotid chemoreceptor can induce, at least in part, progressive morphological changes leading to an increase in the extravascular, reducing the density of the small vessels, and enhancing the volume extravascular by small vessels. This should have the effect of increasing the distance between the vessels and the center of the type I and type II islets that would reduce the PO2 in the tissue and from there an increase in the activity of chemoreceptor. If, as we have proposed, increasing the extracellular volume is the result of the increase in the interstitial space and probably of cell type I and type II it should further increase the blood capillary-tissue distance.


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