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.     

Role of lysosomes in mesenteric arterial lesions of renal hypertensive rats

The acid phosphatase activities of arterial cells in the mesenteric arteries of renal hypertensive rats were investigated by both light and electron microscopy. Light microscopically, strongly positive acid phosphatase reactions were confirmed in endothelial cells, intimal cells, medial cells and adventitial cells of the mesenteric arteries, together with considerable deposition of fibrinoid substance in the intima and media in contrast to the appearance in control rats. Electron microscopically, lysosomes with acid phosphatase-positive reaction products were increased in number in endothelial cells, intimal smooth muscle cells, medial smooth muscle cells and adventitial neutrophils or macrophages. The lysosomes in intimal smooth muscle cells and those which were extracellularly discharged were responsible for lysis of the fibrinoid substance. In the media, acid phosphatase-positive lysosomes of medial cells and extracellularly discharged matrix lysosomes with acid phosphatase-positive reactions were also involved in the hydrolysis of necrotic substances and extracellular matrix. These acid phosphatase-positive reactions were diminished both light and electron microscopically in endothelial cells, intimal cells, medial muscle cells and adventitial cells in the regions of healing arteries where fibrinoid substance had been degradated and the intima showed cellulofibrous thickening. The possible role of this acid phosphatase activation for the clearance of cell debris as well as exudative substances in the healing of damaged arterial tissue was discussed.     

ROLE OF LYSOSOMES IN MESENTERIC ARTERIAL LESIONS OF RENAL HYPERTENSIVE RATS

The acid phosphatase activities of arterial cells in the mesenteric arteries of renal hypertensive rats were investigated by both light and electron microscopy. Light microscopically, strongly positive acid phosphatase reactions were confirmed in endothelial cells, intimal cells, medial cells and adventitial cells of the mesenteric arteries, together with considerable deposition of fibrinoid substance in the intima and media in contrast to the appearance in control rats. Electron microscopically, lysosomes with acid phosphatase-positive reaction products were increased in number in endothelial cells, intimal smooth muscle cells, medial smooth muscle cells and adventitial neutrophils or macrophages. The lysosomes in intimal smooth muscle cells and those which were extracellularly discharged were responsible for lysis of the fibrinoid substance. In the media, acid phosphatase-positive lysosomes of medial cells and extracellularly discharged matrix lysosomes with acid phosphatase-positive reactions were also involved in the hydrolysis of necrotic substances and extracellular matrix. These acid phosphatase-positive reactions were diminished both light and electron microscopically in endothelial cells, intimal cells, medial muscle cells and adventitial cells in the regions of healing arteries where fibrinoid substance had been degradated and the intima showed cellulofibrous thickening. The possible role of this acid phosphatase activation for the clearance of cell debris as well as exudative substances in the healing of damaged arterial tissue was discussed.     

Morphogenesis of plasmatic arterionecrosis as the cause of hypertensive intracerebral hemorrhage

Summary The morphogenesis of the vascular lesions, which were considered to be the immediate cause of hypertensive intracerebral hemorrhage, was morphologically studied in autopsy cases. The direct cause of the hemorrhage was the rupture of the intracerebral microaneuysms resulted from the plasmatic arterionecrosis. The arterionecrosis was predominantly present in the intracerebral arteries of approximately 150 µ diameter, especially in the external branches of the arteriae corporis striati mediae in the putamen, and characterized by medial smooth muscle cell loss, blood plasma insudation in the intima, histolysis of the internal elastic lamina and intimal collagenous fibers, fibrin deposition (fibrinoid degeneration) in the intima, and luminal dilatation. The morphogenesis of the arterionecrosis was the development of histolysis as well as fibrinoid degeneration caused by blood plasma insudation in the wall of the intracerebral arteries with preceding necrosis and loss of medial smooth muscle cells and subsequent fibrous intimal thickening with dilated lumina. Intracerebral microaneurysms were also formed by the plasmatic arterionecrosis in a narrow sense, in which histolysis due to blood plasma insudation had occurred, but fibrin (fibrinoid substance) deposition in the intima had not yet arisen.     

LYSOSOMES IN HEALING PROCESS OF ARTERIAL FIBRINOID DEGENERATION IN HYPERTENSIVE RATS

Twelve 3-week-old, Wistar inbred rats were made hypertensive by bilateral constriction of renal arteries with silver clip. At 3–8 weeks after induction of hypertension, nodular lesions of mesenteric arteries were biopsied, and constricting clips were removed. At 5–28 days after removal of the clips, the animals were killed. Systoric blood pressure of the rats was 200 mm Hg and over before removal of the clips, and decreased at the time when they were sacrificed. Ultrastructurally, modified smooth muscle cells were seen among the fibrinoid substance during healing process of fibrinoid degeneration in the intima. Fine cytoplasmic processes of these cells contained numerous lysosomes. The fibrinoid substance became reticular and reduced its density. The cytoplasmic processes with lysosomes were seen neither in the biopsied specimens nor in the tissues which showed cellulo-fibrous intimal thickening. Lysosomal enzymes were considered to increase in the modified smooth muscle cells during healing process of the fibrinoid degeneration. The enzymes were believed to be discharged extracellularly and to digest the fibrinoid substance partially. The partially dissolved substance might be phagocytized by the modified smooth muscle cells to form vacuoles of a medium electron density.     

The pathogenesis of cerebrovascular lesions in hypertensive rats

In this study we investigated the pathogenesis of hypertensive cerebrovascular lesions by light microscopy, immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. The brains of rats with experimentally induced hypertension exhibited severe edema and intracerebral hemorrhage. Light microscopy of the arteries showed severe medial lesions and the deposition of fibrinoid substance in the intima. Immunohistochemistry showed that intercellular adhesion molecule (ICAM)-1, platelet-endothelial cell adhesion molecule (PECAM)-1, interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha endothelial cell expression was upregulated. Scanning electron microscopy of these arteries revealed the adhesion of neutrophils, monocytes, and a few platelets to endothelial cells, and their invasion of endothelial cell junctions and opened junctions. Transmission electron microscopy showed neutrophil and monocyte adhesion to the endothelial cells and neutrophil and monocyte invasion of endothelial cell junctions, intimal deposition of fibrinoid substance, and severe medial cell injury. Intravenously injected horseradish peroxidase insulated from endothelial cell junctions and, via pinocytotic vesicles, into the subendothelial space. These findings suggest that hypertension activates endothelial cells to increase the expression of adhesion molecules and cytokines, and induces neutrophil and monocyte adhesion and migration, resulting in endothelial cell injury and increased permeability of endothelial cells, which results in hypertensive arterial disease.     

Arterionecrosis of the equine mesentery in naturally occurring endotoxaemia

This report describes the mesenteric arteriolar lesions in a Thoroughbred racehorse with endotoxaemia due to colic. The vascular lesions consisted of a striking loss of medial smooth muscle cells, associated with granular cell debris derived from necrosed muscle cells, plasma insudation, erythrocyte infiltration and the deposition of a fibrinoid substance (fibrinoid degeneration) in the entire arterial wall, possibly produced by the infiltration of blood components through endothelial cell junctions into the arterial wall. The morphology of the mesenteric arteriolar necrosis closely resembled that seen in experimental equine endotoxaemia and in horses that died from colic; it also resembled that of Shiga toxin-induced arteriolar lesions in oedema disease of swine and of the arterionecrosis in human cerebral arteries that may lead to hypertensive intracerebral haemorrhage.     

Light and scanning electron microscopic and immunohistochemical studies on permeability of hypertensive rat mesenteric arteries

Experimental hypertensive rats were intravenously injected with carbon and iron as tracers, and their mesenteric arteries exhibiting hypertensive arterial lesions were observed by light and scanning electron microscopy and immunohistochemistry. Early arterial lesions showing intense medial damages, deposition of fibrinoid substance consisting of fibrin in the intima and/or media, and granulation tissue in the adventitia were characterized by marked insudation of intravenously injected tracers. Scanning electron microscopy demonstrated numerous leukocytes and platelets adhering to endothelial surface, opened endothelial cell junctions, and desquamation of these cells. Immunohistochemistry revealed laminin and low stainability of fibronectin in the subendothelium. Advanced lesions showed deposition of a large amount of fibrinoid substance and no insudation of tracers in the intima, but scanning electron microscopy manifested opening of endothelial cell junctions, desquamation of endothelial cells, and adherence of leukocytes and platelets. Immunohistochemistry revealed fibronectin in the intima and laminin just beneath the endothelium. In the healed lesions disclosing fibrocellular intimal thickening, there was no insudation of tracers. Scanning electron microscopy showed opened endothelial cell junctions, endothelial cell defects, and adherence of leukocytes and platelets. There were fibronectin in the intima and laminin beneath the endothelium. It was suggested that the opening of endothelial cells junctions and desquamation of endothelial cells would be necessary for the arterial increased permeability in hypertensive rats, and that fibrin-fibronectin complex, fibronectin-acid mucopolysaccharide complex, and basement membrane would together inhibit the increased permeability in the mesenteric arteries of hypertensive rats in spite of endothelial cell injuries and their defects.     

LIGHT AND SCANNING ELECTRON MICROSCOPIC AND IMMUNOHISTOCHEMICAL STUDIES ON PERMEABILITY OF HYPERTENSIVE RAT MESENTERIC ARTERIES

Experimental hypertensive rats were intravenously injected with carbon and iron as tracers, and their mesenteric arteries exhibiting hypertensive arterial lesions were observed by light and scanning electron microscopy and immunohistochemistry. Early arterial lesions showing entense medial damages, deposition of fibrinoid substance consisting of fibrin in the intima and/or media, and granulation tissue in the adventitia were characterized by marked insudation of intravenously injected tracers. Scanning electron microscopy demonstrated numerous leukocytes and platelets adhering to endothelial surface, opened endothelial cell junctions, and desquamation of these cells. Immunohistochemistry revealed laminin and low stainability of fibronectin in the subendothelium. Advanced lesions showed deposition of a large amount of fibrinoid substance and no insudation of tracers in the intima, but scanning electron microscopy manifested opening of endothelial cell junctions, desquamation of endothelial cells, and adherence of leukocytes and platelets. Immunohistochemistry revealed fibronectin in the intima and laminin just beneath the endothelium. In the healed lesions disclosing fibrocellular intimal thickening, there was no insudation of tracers. Scanning electron microscopy showed opened endothelial cell junctions, endothelial cell defects, and adherence of leukocytes and platelets. There were fibronectin in the intima and laminin beneath the endothelium. It was suggested that the opening of endothelial ceils junctions and desquamation of endothelial cells would be necessary for the arterial increased permeability in hypertensive rats, and that fibrin-fibronectin complex, fibronectin-acid mucopolysaccharide complex, and basement membrane would together inhibit the increased permeability in the mesenteric arteries of hypertensive rats in spite of endothelial cell injuries and their defects.     

Structural Changes Within the Media of Coronary Arteries Related to Intimal Thickening

From observations on 454 coronary arteries from subjects ranging in age from prematurely newborn to 90 years, six structural patterns of medial smooth muscle are interpreted as representing, or related to, the proliferation and/or migration of medial smooth muscle into intima. By measuring the extent of inner medial circumference occupied by four of the six patterns, it was possible to calculate a numerical value designated the medial proliferatice and / or migratory activity (MP-MA) of each artery. During the first three decades, nonatherosclerotic diffuse intimal thickening was the characteristic intimal process, and during this phase of the arterial maturation span, the MP-MA of the arteries was significantly related to the degree of intimal thickening. Following a peak MP-MA level by the end of the third decade, there was a progressive decrease in the MP-MA level as the incidence and severity of atherosclerotic intimal thickening increased. At advanced stages of atherosclerotic intimal thickening, which were associated with thinning of adjacent media, intimal-medial structural patterns indicating a relationship between medial smooth muscle proliferative activity and the expanding atherosclerotic plaque were also apparent. The observations support the concept that the movement of medial smooth muscle into intima is a critical step preceding and during the evolution of the atherosclerotic plaque.     

Role of lysosomes in coronary artery lesions of hypertensive rats

Electron microscopically the role of acid phosphatase (acid P) positive lysosomes in the pathogenesis of intramyocardial coronary artery lesions of hypertensive rats with bilaterally constricted renal arteries was studied. At 3 postoperative weeks, acid P positive lysosomes were increased in endothelial cells of the coronary arteries, but at 5 weeks and thereafter, they were decreased in number. In the intima, intimal smooth muscle cells with acid P positive lysosomes appeared at 3 postoperative weeks, but their number remained small as late as 9 postoperative weeks. The internal elastic lamina was fragmented into amorphous masses from 3 postoperative weeks, at 5 weeks and thereafter the fragmentation and disruption became severer, and at 9 weeks the lamina disappeared because of marked disruption. At 3 postoperative weeks, acid P positive extracellular lysosomes were observed in the gaps of the fragmented internal elastic lamina. At 5 weeks and thereafter, extracellular lysosomes and attenuated processes of medial smooth muscle cells with lysosomes were seen extending through the gaps of the fragmented internal elastic lamina. Necrosis of these extending cell processes and lysosomes remaining after the necrosis were observed. The findings suggested that the fragmentation and lytic change of the internal elastic lamina observed in hypertensive rat intramyocardial coronary arteries might be induced by extracellular lysosomes discharged not only from endothelial cells and intimal smooth muscle cells but also from the extending processes of medial smooth muscle cells into the gaps of the internal elastic lamina.     

Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening

The organization of actin, vimentin, and desmin in smooth muscle cells of rat aortic media and intima under normal conditions and 15 or 75 days after endothelial injury has been studied by means of electron microscopy, indirect immunofluorescence, densitometric analysis of sodium dodecyl sulfate-polyacrylamide gels, isoelectric focusing, and bidimensional gels. In the normal aortic media, practically all smooth muscle cells contain vimentin, and about 50% of them contain, in addition, desmin; upon analysis of actin isotypes by bidimensional gels, smooth muscle cells show a predominance of alpha-actin, some beta-actin, and very little gamma-actin. Fifteen days after endothelial injury, cells that have migrated into the intima contain decreased amounts of actin and desmin and increased amounts of vimentin compared with normal medial smooth muscle cells. Moreover, beta-actin becomes the predominant actin isotype and significant amounts of gamma-actin appear, whereas alpha-actin decreases. Seventy-five days after endothelial injury, regenerated endothelial cells have repaired the injury. Intimal smooth muscle cells are less numerous than 15 days after injury, and the organization of their cytoskeletal elements has reverted almost to normal conditions. At both 15 and 75 days after endothelial injury, no significant changes of cytoskeletal elements are seen in the aortic media underlying intimal thickenings.     

Fibrinoid degeneration and increased vascular permeability induced by renal lysosomal contents

Summary The effect of the lysosomal contents of hog kidney cortex, especially of the fraction not bound by concanavalin A (Fraction A) on the permeability of the coronary and cerebral arteries of rats was studied ultrastructurally using H.R. peroxidase. This fraction was devoid of renin activity by bioassay.The coronary arteries of the experimental rats displayed fibrinoid degeneration: e.g., degeneration and disappearance of medial smooth muscle cells and deposition of electron dense materials containing fibrin. A large amount of reaction product of peroxidase was present in the subendothelial space and media where fibrinoid degeneration was evident. Transendothelial passage of the marker occurred by both junctional and vesicular transport. There was no evidence of separation or discontinuity of the endothelial cells. Occasionally, increased permeability of the intima was noted in the coronary arteries without medial damage. By contrast, neither fibrinoid degeneration nor increased permeability was noted in the cerebral arteries. The difference in the response of the two arteries seems attributable to the barrier effect of cerebral arterial intima.     

ROLE OF LYSOSOMES IN CORONARY ARTERY LESIONS OF HYPERTENSIVE RATS

Electron microscopically the role of acid phosphatase (acid P) positive lysosomes in the pathoǵenesis of intramyocardial coronary artery lesions of hypertensive rats with bilaterally constricted renal arteries was studied. At 3 postoperative weeks, acid P positive lysosomes were increased in endothelial cells of the coronary arteries, but at 5 weeks and thereafter, they were decreased in number. In the intima, intimal smooth muscle cells with acid P positive lysosomes appeared at 3 postoperative weeks, but their number remained small as late as 9 postoperative weeks. The internal elastic lamina was fraǵmented into amorphous masses from 3 postoperative weeks, at 5 weeks and thereafter the fraǵmentation and disruption became severer, and at 9 weeks the lamina disappeared because of marked disruption. At 3 postoperative weeks, acid P positive extracellular lysosomes were observed in the ǵaps of the fraǵmented internal elastic lamina. At 5 weeks and thereafter, extracellular lysosomes and attenuated processes of medial smooth muscle cells with lysosomes were seen extending through the ǵaps of the fraǵmented internal elastic lamina. Necrosis of these extendinǵ cell processes and lysosomes remaininǵ after the necrosis were observed. The findinǵs suǵǵested that the fraǵmentation and lytic chanǵe of the internal elastic lamina observed in hypertensive rat intramyocardial coronary arteries might be induced by extracellular lysosomes discharǵed not only from endothelial cells and intimal smooth muscle cells but also from the extendinǵ processes of medial smooth muscle cells into the gaps of the internal elastic lamina. ACTA PATHOL. JPN. 36: 1529-1536, 1986.     

Ultrastructural localization of peroxidase in atherosclerotic lesions of pigeons.

Atherosclerotic lesions are known to have metabolic alterations which are associated with progressive lipid accumulation. Among the changes, lysosomal enzyme activity has been extensively characterized and at the ultrastructural level has been correlated with the amount of foam cell lipid. In a fashion paralleling lysosomal change, artery wall peroxidase activity is also altered during disease progression. The present study focuses upon the ultrastructural localization of peroxidase activity in atherosclerotic lesions of the aorta and coronary arteries from White Carneau pigeons fed a cholesterol-supplemented (0.3%) diet for 3 years. This resulted in fibrous lesions, rich in smooth muscle cells. The birds were necropsied by perfusion fixation, and peroxidase cytochemistry was carried out using the diaminobenzidine reaction. Peroxidase activity was found within endothelial cells and smooth muscle cells in both the media and intima, but cytochemically demonstrable activity was not found in macrophage foam cells. Peroxidase was localized within the nuclear envelope and endoplasmic reticulum, especially within cells that had lipid inclusions. The degree of peroxidase positivity varied within and among the arteries. In nonlesion regions of the aorta 20% of medial smooth muscle cells was peroxidase positive; the value for coronary artery smooth muscle cells was less. The peroxidase activity within aortic lesions was increased with 44% of intimal smooth muscle cells being positive. Notably, 85-90% of the lipid-containing intimal smooth muscle cells were positive. In contrast, intimal smooth muscle cells in the coronary artery lacked peroxidase reaction product, even in cells containing lipid. We conclude from these studies that aortic lesions contain a cytochemically differentiated subset of lipid-containing, peroxidase-positive smooth muscle cells; but coronary lesions lack a comparable subset of smooth muscle cells.     

An electron microscopic study of plasmatic arterionecrosis in the human cerebral arteries

Summary An electron microscopic study of the intracerebral arteries from 9 hypertensive cases was performed in order to elucidate the morphogenesis of the plasmatic arterionecrosis which was considered to be the direct cause of hypertensive intracerebral hemorrhage. In the preceding stage of the arterial lesions, marked necrosis of medial smooth muscle cells and increase of basement membrane-like substance in the intima and media were observed. The lumina of these arteries were slightly dilated. The dilatation and hemodynamic factors were supposed to cause endothelial injury resulting in blood plasma insudation into the intima through the opened spaces between endothelial cells. The insudated blood plasma dispersed and dissolved the basement membrane-like substance, collagen and elastic fibers in the arterial wall, leading to the development of the plasmatic arterionecrosis.This study was supported by a Grant-in-Aid for Scientific Research of the Japanese Ministry of Education (No. 857052).     

Kinetics of cellular proliferation after arterial injury. II. Inhibition of smooth muscle growth by heparin

Heparin inhibits intimal thickening after arterial injury. Whether this effect is due to inhibition of medial smooth muscle cell (SMC) migration, SMC proliferation in the intima, or synthesis and deposition of connective tissue has not been evident. In this study we have investigated these possibilities in a rat carotid balloon injury model. Heparin (0.3 mg/kg/hour) was administered intravenously by means of osmotic pumps to experimental animals, and controls received lactated Ringer's solution. Smooth muscle proliferation (thymidine index), intimal smooth muscle accumulation, and endothelial regeneration were measured at intervals between 0 and 28 days. Total smooth muscle growth as determined biochemically at 14 days was markedly inhibited by heparin if the pumps were placed 24 hours before or at the time of injury and less so if inserted 48 or 96 hours after injury. SMC thymidine indices were maximal in the media at 4 days and in the intima at 7 days for injured arteries of both heparin-treated and control rats; at each time point SMC proliferation and intimal thickening were less in heparin-treated rats. The volume of connective tissue in the intima was the same in both groups at 28 days. Medial SMC migration into the intima was diminished by heparin treatment, but endothelial regeneration was not affected. These results support the hypothesis that heparin is a specific inhibitor of SMC migration and proliferation and is most effective if started before SMC enter S-phase.     

Endothelial regeneration. II. Restitution of endothelial continuity

With a modified balloon catheter the endothelium of rat thoracic aortae was completely removed to study the interaction between two important responses of the vessel wall to intimal injury: endothelial regeneration and formation of an intimal fibrocellular thickening. Endothelial cells deriving from the uninjured intercostal arteries regenerated by migration followed by proliferation and proceeded as a continuous sheet at a rate of approximately 0.07 mm. per day in the circumferential direction and approximately 6 times faster in the axial direction. Smooth muscle cells appeared in the intima only in areas which were not covered by regenerating endothelium 7 days after injury. The smooth muscle cells formed a multilayered fibrocellular intimal lesion which reached the maximal thickness after 3 weeks. The continuous sheet of regenerating endothelium covered the intimal smooth muscle cells at a slower rate; 6 weeks after injury large areas located most distant from the source of regenerating endothelium still showed modified smooth muscle cells lining the lumen. However, platelets did not adhere to these smooth muscle cells, and the total amount of intimal thickening did not increase between 3 and 6 weeks after injury. We conclude that, in response to intimal injury, endothelial regeneration precedes the accumulation of intimal smooth muscle cells, and that injured intimal areas, which are rapidly covered by continuous endothelium, are protected from the development of a fibrocellular intimal lesion.     

Renal proliferative arteriopathies and associated glomerular changes: A light and electron microscopic study

This presentation reports the light and electron microscopic findings relating to the vascular and glomerular changes in the kidney in a series of 25 patients having malignant hypertension, the hemolytic-uremic syndrome, scleroderma, or toxemia of pregnancy. The pathologic changes were generally similar in each of the diseases studied, the changes being related more to the severity and duration of injury than to the specific disease. Vascular narrowing was due mainly to intimal thickening, and by light microscopy the lesions were categorized as onionskin, mucinous, or fibrous with or without associated elastosis. Intimal erythrocyte extravasation, fibrinoid necrosis, and luminal thrombosis were also seen. Electron microscopy provided additional morphologic information: Myointimal cells were found to be the cellular component in each type of intimal thickening; it was possible to distinguish collagen from large intimal accumulations of basement membrane material; mucinous intimal material was characterized ultrastructurally; and fibrinoid necrosis was identified as a lesion inconstantly associated with cellular necrosis and consisting mainly of fibrinoid material and small deposits of fibrin. It seems likely that there is a common pathogenesis for intimal thickening in a variety of diseases and that this involves endothelial cell damage and increased permeability, leakage of serum and crythrocytes into the intima, and a healing reaction of the vessel wall developing from migration of smooth muscle cells into the intima with subsequent myointimal cell proliferation and fibrogenesis.A common glomerular change in all diseases studied was a striking accumulation of electron lucent material between the endothelium and the lamina densa of the basement membrane. This lesion was interpreted as a manifestation of acute ischemia.     

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.