SCANNING AND TRANSMISSION ELECTRON MICROSCOPIC STUDY ON THE CEREBRAL ARTERIAL ENDOTHELIUM OF EXPERIMENTALLY HYPERTENSIVE RATS FED AN ATHEROGENIC DIET

In order to clarify the roles of hypertension and hypercholesterolemia in atherogenesis, the cerebral arterial endothelium of experimentally hypertensive female rats fed an atherogenic diet were investigated by scanning and transmission electron microscopy. The hypertension was induced by constriction of the bilateral renal arteries. In both hypertensive groups, group I (hypertension+hypercholesterolemia) and group III (hypertension), many endothelial cells covered with numerous microvillous projections were observed. Pinocytotic vesicles and caveolae were also increased in these endothelial cells. On the other hand, in group II loaded with only hypercholesterolemia, microvillous projections on the endothelial cells tended to be increased, but its grade seemed to be lower than those of the hypertensive groups. These findings suggest that hypertension appears to be more effective than hypercholesterolemia in the cause of the increase of microvilli on the endothelial cell surfaces and the increase may be related to increased permeability in the cerebral arteries.     

ON THE MORPHOGENESIS OF MASSIVE CEREBRAL HEMORRHAGE IN EXPERIMENTAL HYPERTENSIVE RATS

The morphogenesis of massive cerebral hemorrhagic lesions was studied in 6 experimental hypertensive rats. Hemorrhage due to rupture of arteries caused by hypertensive arterial lesions (plasmatic arterionecrosis) was found in the middle cerebral arteries in the subarachnoid space and immediately after their penetrating into the cerebral parenchyma. This primary hemorrhage induced, through circulatory disturbances, secondary bleedings of small vessels and veins, which were all combined to give rise to a massive hemorrhagic lesion. The hypertensive arterial lesions, which were the direct cause of the cerebral hemorrhage, were constituted by necrosis and disappearance of smooth muscle cells and blood plasma infiltration in the media, blood plasma infiltration, especially deposition of fibrin, having periodic cross striation of about 200 Å (fibrinoid degeneration) in the intima, and dissolution and disappearance of the internal elastic lamina.     

A case report of basal cell adenoma showing elastic fiber (elastin-basement membrane complex) formation of the submandibular gland

A biopsy case of basal cell adenoma of the submandibular gland was reported in a 15-year-old boy. The tumor was pigeon's egg-sized, spherical in shape and encapsulated by fibrous tissue, and its cut-surface was grayish white. Histologic feature of this neoplasm was a trabecular or tubular monomorphic adenoma with well-developed elastic fibers (elastin-basement membrane complex) in the interstitial tissue. Electron microscopy disclosed 4 kinds of tumor cells, that is, secreting cells, squamous cell-like cells with tonofibrils and tonofilaments, clear cells with a few filaments, and myoepithelial cells. The interstitium contained elastin, collagen fibrils and basement membrane-like substance. Possible production of elastic fibers by the myoepithelial cells of this adenoma was discussed.     

ULTRASTRUCTURAL OBSERVATIONS ON BIFURCATIONS IN RAT CEREBRAL ARTERIES

The bifurcation pads ("valve-like projections") in the anterior cerebral arteries of rats with long-term hypertension were studied electron microscopically. The rats ranging in age from 2 to 10 months were sacrificed after bilateral renal artery constriction at 5-week-old. In the bifurcation pads (intimal pads) of hypertensive rats, smooth muscle cell damage first appeared in the roots of the pads as well as underlying media in the form of granular, vesicular, and somewhat tubular structures (200–1500 Å in diameter). Thereafter, with a lapse in time after the operation, these abnormal substances increased around the smooth muscle cells which were arranged in the marginal zones of the pads. Deeply arranged intimal smooth muscle cells which were embedded in an abundance of ground substances were only damaged in rats with very long-term hypertension. The medial smooth muscle cells beneath the pads manifested lesions which were more marked and diffuse than in the intima. These smooth muscle cells were bizarrely atrophied and abnormal substances which might be derived from necrotic smooth muscle cells were found around them. Basement membrane-like substances, either thick or multilaminated, were also present around them.     

ENDOTHELIAL CHANGES OF HYPERTENSIVE RAT MESENTERIC ARTERIES

The mesenteric arteries of hypertensive rats with bilaterally constricted renal arteries were observed by light, scanning electron and transmission electron microscopy. In the early stage of hypertensive arterial lesions, many leukocytes adhered to the endothelial surface, and large or small and polygonal endothelial cells were irregularly arranged. Sporadically brightened and atrophied endothelial cells were distributed on the injured surface. These atrophied cells were transmission electron microscopically confirmed to have undergone coagulation necrosis. In the surrounding of the atrophied cells were observed opened endothelial cell junctions and enlarged intercellular spaces to which many leukocytes and platelets adhered. Because of loosening of connection with neighboring cells, atrophied endothelial cells became solitary or being denuded. Opened endothelial cell junctions were also observed between the uninjured endothelial cells as well as in areas penetrated by leukocytic pseudopods. Where light microscopy disclosed the deposition of a large amount of fibrinoid substance in the intima and media, scanning electron microscopy showed opened endothelial cell junctions and denudation of endothelial cells. From the results of the present experimental study, it was suggested that in the genesis of the hypertensive rat arterial lesions, the degeneration, necrosis and denudation of endothelial cells, opened endothelial cell junctions between these cells, and insudation of blood plasma through the opened junctions or denuded areas might play important roles.     

Endothelial changes of hypertensive rat mesenteric arteries

The mesenteric arteries of hypertensive rats with bilaterally constricted renal arteries were observed by light, scanning electron and transmission electron microscopy. In the early stage of hypertensive arterial lesions, many leukocytes adhered to the endothelial surface, and large or small and polygonal endothelial cells were irregularly arranged. Sporadically brightened and atrophied endothelial cells were distributed on the injured surface. These atrophied cells were transmission electron microscopically confirmed to have undergone coagulation necrosis. In the surrounding of the atrophied cells were observed opened endothelial cell junctions and enlarged intercellular spaces to which many leukocytes and platelets adhered. Because of loosening of connection with neighboring cells, atrophied endothelial cells became solitary or being denuded. Opened endothelial cell junctions were also observed between the uninjured endothelial cells as well as in areas penetrated by leukocytic pseudopods. Where light microscopy disclosed the deposition of a large amount of fibrinoid substance in the intima and media, scanning electron microscopy showed opened endothelial cell junctions and denudation of endothelial cells. From the results of the present experimental study, it was suggested that in the genesis of the hypertensive rat arterial lesions, the degeneration, necrosis and denudation of endothelial cells, opened endothelial cell junctions between these cells, and insudation of blood plasma through the opened junctions or denuded areas might play important roles.     

Studies on the healing of arterial lesions in experimental hypertension

Summary Rats made hypertensive by bilaterally constricting their renal arteries were intermittently given antihypertensive drugs to cause their blood pressure to fluctuate; the intima of their mesenteric arteries was then investigated electron microscopically. The intimal fibrinoid degeneration showed a much weaker tendency to heal than that of the previously reported rats treated continuously with antihypertensive drugs (Kojimahara et al., 1971), and the arteries showed marked dysoria associated with endothelial injury and thrombus formation. Endothelial cells that had migrated from the endothelium into the subendothelial space became intimal cell, which after proliferation by mitosis, formed myofilaments in their cytoplasm, turning into fibroblast-like smooth muscle cells (modified smooth muscle cells) in the intima. Thus some of the smooth muscle cells that proliferated in the intima and took part in the organization of the intimal fibrinoid substance were considered to be derived from endothelial cells.