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An ultrastructural study of the vascular alterations within the carotid bodies of spontaneously hypertensive rats (SHR)
Exp. Path. 27, 195-200 (1985) Institute of Pathology, District Hospital, Karl-Marx-Stadt (Head: Dr. sc. med. H. WALLER) Martin Luther University Halle-Wittenberg, Institute of Pathology (Head: Prof. Dr. sc. med. D. STILLER)
An ultrastructural study of the vascular alterations within the carotid bodies of spontaneously hypertensive rats (SHR) By J.-O. HABECK and H. J. HOLZHAUSEN With 2 figures (Received December 2, 1983)
A.ddress for correspondence: Dr. J.-O. HABECK, Institut fUr Pathologie, Bezirkskrankenhaus, BiirgerstraBe 2, DDR - 9003 Karl-Marx-Stadt Key wo rds: spontaneously hypertensive rats; earotid bodies; arterioles; ultrastructure
Summary Electron microscopic studies of the fine structural changes of the arterioles within the carotid bodies of spontaneously hypertensive rats (SHR) in the established phase of hypertension revealed partly hyperplastic endothelial cells. In the subendothelial space a multiplication of the basal laminae was observed often of a whirl-like shape. The smooth muscle cells of the media were hypertrophied, bizarre and with numerous projections. They exhibited a marked increase in cell organelles. The extracellular space was extensively enlarged and partly vacuolated. It contained a basement membrane-like material which was connected with the basal laminae of the myocytes. All these alterations produced a pad-like thickening of the arteriolar wall which narrowed the vessel lumen. These findings and their possible effects on carotid body function are discussed.
Introduction Light-microscopic features of vascular alterations in the carotid bodies of spontaneously hypertensive rats (SHR) have already been described in a previous paper (8). Vascular changes were observed for the first time in 0-6 weeks old SHR and regularly in animals of this strain older than 1 year. These alterations were the result of high arterial blood pressure (7,8,11, 12). In the present study these lesions were examined electron-microscopically.
Material and
J;[ethods
The investigations were performed on 3 carotid bodies of normotensive Wistar rats of a randombred strain (20 and 30 weeks old, systolic blood pressure 105-110 mm Hg) and on 2 carotid bodies of spontaneously hypertensive rats of the OKAMOTO-AOKI-strain (20) (35 weeks old, systolic blood pressure 170-210 mm Hg). After killing the anaesthetized animals by bleeding the carotid bifurcations were removed immediately and fixed in 3 % phosphate buffered glutaraldehyde solution for 1 h. The tissue was then fixed in 1 % OS04' dehydrated in ascending concentrations of ethanol and embedded in Durcupan ACl\L For a first light-microscopic orientation semithin sections were made and stained with toluidine blue. Then ultrathin sections were prepared with the ultramicrotome "Ultracut" (Reichert-Jung) and stained with uranyl acetate and lead citrate and were subsequently examined under an electron-microscope SEM 3-2 (VEB Werk fiir Fernsehelektronik Berlin).
13*
195
Fig. 1. Spontaneously hypertensive rat. Bigger arterioles (first or second order branches of the carotid body artery). a) Vessel lumen (1.,.). The media is widened to a large extent. The myocytes (MI-M4) are hypertrophied and of an irregular shape which is caused by numerous processes (P). One cell (Ml) contains an increased number of organelles (mitochondria and rough endoplasmic reti-
196
Exp. Path. 27 (1985) 4
Fig. 2. Spontaneously hypertensive rat. a) Detail of fig. 1 a. Endothelial cell (E) with great Golgi apparatus (G). The endothelial cells are connected by junctional complexes (J). Basement membranelike substances in the subendothelial space (S). Processes of the myocytes (P) and detached basal lamina in the media. The extracellular space is vacuolated and contains basement membrane-like material (B). x 20,000. b) Smooth muscle cell (M) with activated Golgi apparatus (G). Endothelial cell (E). Branching of the basal lamina in the subendothelial space. x 20,000. c) Endothelial cell (E) with a centriole. Conglomerate of basement membrane-like substances (B) in the subendothelial space. x 20,000.
culum). Massive enlargement of the transparent extracellular space of the media (V). The vacuolated
extracellular space contains basement membrane-like material. Process of a myocyte (P). Endothelial
cells (E). Adventitia (A). x 5,000. b) The extracellular space of the media is massively vacuolated. Numerous processes of myocytes (P) and basement membrane-like material are also demonstrable here. Hypertrophied smooth muscle cell of a bizarre shape (lVI). Parts of endothelial cells (E). x 5,000.
Exp. Path. 27 (1985) 4
197
Results 1. Normotensive Wistar rats: Usually small arterioles or metarterioles were observed in the sections of the carotid bodies. Only one layer of smooth muscle cells enveloped the metarterioles incompletely. In one carotid body a bigger arteriole was studied more closely. The wall consisted of three loosely arranged layers of smooth muscle cells enveloped by a basal lamina. In the myocytes numerous pinocytic vesicles were present on the cell membrane and sometimes an increase in the density of the myofilaments was observed. An internal elastic lamina was partly present in the subendothelial space. The endothelial cells were situated on a basal lamina and connected by junctional complexes. The adventitia contained collagen bundles and single small processes of fibrocytes. 2. Spontaneously hypertensive rats (SHR): The wall of the big arterioles showed an extensive pad-like thickening (figs. 1 a, b). The smooth muscle cells of the media were hypertrophied, bizarre and with numerous projections (fig. 1). Many myocytes exhibited a marked increase in cell organelles. Mitochondria and rough endoplasmic reticulum were enlarged (fig. 1 a) and the Golgi apparatus was increased, too (fig. 2 b). The smooth muscle cells were partly surrounded by a basal lamina which was often detached from the cells. In the extracellular space numerous small processes of myocytes were demonstrable (figs. 1 b, 2 a). The extracellular space was extensively enlarged and partly vacuolated. It contained a thin, filament- and basement membrane-like material which was in connection with the basal lamina of the myocytes (figs. 1, 2 a). Moreover, there were partly hyperplastic endothelial cells (fig. 2 a) which were connected by junctional complexes. In the subendothelial space a multiplication of the basal laminae was visible, often of a whirl-like shape (fig. 2). There were no gaps in the endothelium. An internal elastic lamina could not be demonstrated.
Discussion Our ultrastructural findings of the arterioles within the carotid bodies of normotensive rats are identical with those of other authors (4, 18). Arterioles and metarterioles of other organs show a similar structure (5, 25, 26). In previous light-microscopic studies we found a pad-like thickening of the arteriolar wall within the glomus caroticum of SHR older than 5 weeks (7, 8). These pad-like areas show extensive alterations of the media in the study presented here. We found that hypertrophied myocytes exhibit an increased content of organelles and develop numerous irregular processes. Within this study we could not prove, however, that this is a true proliferation of the smooth muscle cells themselves. Apparently the enlargement of the media is caused by an extension of the extracellular space between the myocytes. The extracellular space seems to be transparent and contains thin, filamentand basement membrane-like substances. In previous light-microscopic observations we found a high amount of acid mucopolysaccharides in these pad-like areas of the intraglomic arterioles (8). It is well known that mucopolysaccharides are dissolved to a large extent by fixation techniques. Therefore, the vacuolisation of the extracellular space may be due to the dissolved acid mucopolysaccharides. The production of acid mucopolysaccharides by myocytes is well known (10, 14). In several forms of hypertension an increased content of acid mucopolysaccharides is observed in the media (9, 16, 17). The described alterations of the media of arterioles within the carotid bodies of SHR are of the same nature as the findings on arterioles in other organs caused by experimental hypertension (1,2,6, 15, 27, 28). Separation of the subendothelial space and multiplication of basement membrane-like material (1, 3, 13) also occurred in this area. At present one can only speculate about the functional effects of the vascular changes narrowing the lumina to a different extent. A reduced blood flow and/or a disturbed flow distribution in or through the glomus caroticum might be one result. A stimulation of the chemoreceptive tissue by ischemic hypoxia is therefore possible. On the other hand the blood
198
Exp. Path. 27 (1985) 4
vessels of the carotid bodies are innervated by sympathetic and parasympathetic nerves (19). The distribution of these perivascular nerves makes it possible that both autonomic inputs are capable of modifying carotid body blood flow (21, 22). The wall of the intraglomic arterioles [first or second order branches of the carotid body artery (18)] is strongly altered in SHR in the established phase of hypertension. A different reaction of these vessels on nervous stimulation followed by a disturbance of the vascular autoregulation of the carotid body is also imaginable. Several functional studies showed a varied function of the peripheral arterial chemoreceptors in SHR in the established phase of hypertension (11,12,23,24). The findings on the vascular system of the carotid bodies of SHR which are presented in this study might be one cause. But there are also some other possibilities for the interpretation of these phenomena (11, 12).
Acknowledgement We wish to thank Mrs. G. ENTER for her help in the preparation of the English text.
Literature 1. AMANO, S., and F. HAZAMA, Electron microscopic study of vascular changes in SHR. Jap. Heart J. 16, 299-301 (1975). 2. BACKWINKEL, K. P., H. THEMANN, G. SCHMITT und W. H. HAUSS, Elektronenmikroskopische
Untersuchungen fiber das Verhalten der glatten Muskelzellen in der Arterienwand. Virchows Arch. A 359,171-184 (1973). 3. BECKER, C. H., D. MATTIIIAS, E. ENGLER, H. J. HERRMANN, K. HECHT und CH. KREHER, Ultrastrukturelle Befunde an der Lamina elastica interna und ihrer Umgebung in Arteriolen von Ratten mit verschiedenen experimentellen Hypertonieformen. Exp. Path. 10, 40-56
(1974). 4. BOCK, P., Das Glomus caroticum der Maus. Springer Verlag, Berlin-Gottingen-New York 1973.
5. CAESAH, R., Gefii.Be und Herz im elektronenmikroskopischen Bild. In: M. STAEMMLER, Lehrbuch der speziellen pathologischen Anatomie. Erganzungsband 1. 1. Hii.lfte. De Gruyter, Berlin 1969. 6. GREDITZER, H. G., and V. W. FISCHER, A sequential ultrastructural study of different arteries in the hypertensive rat. Exp. Mol. Pathol. 29, 12-28 (1978). 7. HABECK, .J.-O., A. HONIG, C. PFEIFFER and M. SCHMIDT, The carotid bodies in spontaneously hypertensive (SHR) and normotensive rats. - A study concerning size, location and blood supply. Anat. Anz. 150, 374-384 (1981). 8. - CH. HUCKSTORF, and A. HONIG, Influence of age on the carotid bodies of spontaneously hypertensive (SHR) and normotensive rats. - II. Alterations of the vascular wall. Exp. Path. 27,
79-89 (1985).
9. HADJIISKY, P., and N. PEYRI, Hypertensive arterial disease and atherogenesis. Part. 1. Intimal changes in the o\~ spontaneously hypertensive rat (SHR). Atherosclerosis 44, 181-199 (1982). 10. HAUSS, W. H., Uber die Rolle des l\fesenchyms in der Genese der Arteriosklerose. Virchows Arch. A 359, 135-156 (1973). 11. HONIG, A., J.-O. HABECK, C. PFEIFFEH, M. SCHMIDT, C. HUCKSTORF, H. ROTTER and P. ECKERMANN, The carotid bodies of spontaneously hypertensive rats (SHR): A functional and morphologic study. Acta bioI. med. germ. 40, 1021-1030 (1981). 12. - Role of the arterial ehemoreeeptors in the reflex control of renal function and body fluid volumes in acute arterial hypoxia. In: H. ACKER and R. G. O'REGAN (eds.): Physiology of the Peripheral Arterial Chemoreceptors; chapter 14. Elsevier Biomedical Press!N orth- Holland, Amsterdam 1983, pp. 395-429. 13. HORI, S., T. NISHIDA, Y.MUIL\I, :VI. POMEROY and N. MUKAI, Ultrastructural studies on choroidal vessels in streptozotocin-diabetic and spontaneously hypertensive rats. Res. Comm. Chern. Pathol. Pharm. 29, 211-228 (1980). 14. JURUKO\VA, Z., und H. P. ROIIR, Beitrag zur Bildung bindegewebiger Matrix in glatten Muskelzellen. Pathol. europ. 3, .551--570 (1968). 15. KEHENYI, T., and I. HUTTNEH, Morphological changes of small muscular-type vessels and arterioles under the influence of various injuries. In: H. JELLINEK (Ed.): Arterial Lesions and Arteriosclerosis. Akademiai Kiado, Budapest 1974. 16. KUNZ, J., Pathologie der Arterienwand. VEB Verlag Yolk und Gesundheit, Berlin 1975. 17. MATTHIAS, D., V. MOHlTZ, E. ENGLER und C. H. BECKER, Histomorphologische GefaB- und Organbefunde und deren Abhiingigkeit vom Alter bei spontan hypertonen Ratten einer Linie des OKAMOTO-AOKI-Stammes. Dt. Gesundh.wesen 35, 1630-1638 (1980). 18. McDONALD, D. M., and D. T. LARUE, The ultrastructure and connections of blood vessels supplying the rat carotid body and carotid sinus. J. Neurocytol. 12, 117-153 (1983). Exp. Path. 27( 1985) 4
199
19. Me DONALD, D. M., A morphometric analysis of blood vessels and perivascular nerves in the rat carotid body. J. Neurocytol. 12, 155-199 (1983). 20. OKAMOTO, K., and K. AOKI, Development of a strain of spontaneously hypertensive rats. Japan. Circul. J. 27, 282-293 (1963).
21. O'REGAN, R. G., Control of carotid body chemoreceptors by autonomic nerves. Irish J. Med. Sci.
146, 199-205 (1977).
22. 23. 24. 25. 26. 27. 28.
Responses of carotid body chemosensory activity and blood flow to stimulation of sympathetic nerves in the cat. J. Physiol. 315, 81-98 (1981). PRZYBYLSKI, J., and W. BROZYNA, Reduced blood pressure response to carotid body chemoreceptor stimulation in spontaneously hypertensive rats. Acta Physiol. Pol. 32, 117-120 (1981). - A. TRZEBSKI, T. CZYZEWSKI, and J. J ODKOWSKI, Responses to hyperoxia, hypoxia, hypercapnia and almitrine in spontaneously hypertensive rats. Bull. europ. Physiopath. resp. 18 (Suppl. 4), 145-154 (1982). REALE, E., und H. RusKA, Die Feinstruktur der GefaBwande. Angiologica 2, 314-366 (1965). ROGGENDORF, W., and J. CERvos-NAVARRO, Ultrastructure of arterioles in the cat brain. Cell Tiss. Res. 178, 495-515 (1977). SPIRO, D., R. G. LATTES and J. WIEXER, The cellular pathology of experimental hypertension. I. Hyperplastic arteriolar-sclerosis. Amer. J. Path. 47, 19-49 (1965). TAKEBAYASHI, S., Ultrastructural studies on arteriolar lesions in experimental hypertension. J. Electron. Microsc. 19, 17-31 (1970).
200
Exp. Path. 27 (1985) 4
An ultrastructural study of the vascular alterations within the carotid bodies of spontaneously hypertensive rats (SHR) By J.-O. HABECK and H. J. HOLZHAUSEN With 2 figures (Received December 2, 1983)
A.ddress for correspondence: Dr. J.-O. HABECK, Institut fUr Pathologie, Bezirkskrankenhaus, BiirgerstraBe 2, DDR - 9003 Karl-Marx-Stadt Key wo rds: spontaneously hypertensive rats; earotid bodies; arterioles; ultrastructure
Summary Electron microscopic studies of the fine structural changes of the arterioles within the carotid bodies of spontaneously hypertensive rats (SHR) in the established phase of hypertension revealed partly hyperplastic endothelial cells. In the subendothelial space a multiplication of the basal laminae was observed often of a whirl-like shape. The smooth muscle cells of the media were hypertrophied, bizarre and with numerous projections. They exhibited a marked increase in cell organelles. The extracellular space was extensively enlarged and partly vacuolated. It contained a basement membrane-like material which was connected with the basal laminae of the myocytes. All these alterations produced a pad-like thickening of the arteriolar wall which narrowed the vessel lumen. These findings and their possible effects on carotid body function are discussed.
Introduction Light-microscopic features of vascular alterations in the carotid bodies of spontaneously hypertensive rats (SHR) have already been described in a previous paper (8). Vascular changes were observed for the first time in 0-6 weeks old SHR and regularly in animals of this strain older than 1 year. These alterations were the result of high arterial blood pressure (7,8,11, 12). In the present study these lesions were examined electron-microscopically.
Material and
J;[ethods
The investigations were performed on 3 carotid bodies of normotensive Wistar rats of a randombred strain (20 and 30 weeks old, systolic blood pressure 105-110 mm Hg) and on 2 carotid bodies of spontaneously hypertensive rats of the OKAMOTO-AOKI-strain (20) (35 weeks old, systolic blood pressure 170-210 mm Hg). After killing the anaesthetized animals by bleeding the carotid bifurcations were removed immediately and fixed in 3 % phosphate buffered glutaraldehyde solution for 1 h. The tissue was then fixed in 1 % OS04' dehydrated in ascending concentrations of ethanol and embedded in Durcupan ACl\L For a first light-microscopic orientation semithin sections were made and stained with toluidine blue. Then ultrathin sections were prepared with the ultramicrotome "Ultracut" (Reichert-Jung) and stained with uranyl acetate and lead citrate and were subsequently examined under an electron-microscope SEM 3-2 (VEB Werk fiir Fernsehelektronik Berlin).
13*
195
Fig. 1. Spontaneously hypertensive rat. Bigger arterioles (first or second order branches of the carotid body artery). a) Vessel lumen (1.,.). The media is widened to a large extent. The myocytes (MI-M4) are hypertrophied and of an irregular shape which is caused by numerous processes (P). One cell (Ml) contains an increased number of organelles (mitochondria and rough endoplasmic reti-
196
Exp. Path. 27 (1985) 4
Fig. 2. Spontaneously hypertensive rat. a) Detail of fig. 1 a. Endothelial cell (E) with great Golgi apparatus (G). The endothelial cells are connected by junctional complexes (J). Basement membranelike substances in the subendothelial space (S). Processes of the myocytes (P) and detached basal lamina in the media. The extracellular space is vacuolated and contains basement membrane-like material (B). x 20,000. b) Smooth muscle cell (M) with activated Golgi apparatus (G). Endothelial cell (E). Branching of the basal lamina in the subendothelial space. x 20,000. c) Endothelial cell (E) with a centriole. Conglomerate of basement membrane-like substances (B) in the subendothelial space. x 20,000.
culum). Massive enlargement of the transparent extracellular space of the media (V). The vacuolated
extracellular space contains basement membrane-like material. Process of a myocyte (P). Endothelial
cells (E). Adventitia (A). x 5,000. b) The extracellular space of the media is massively vacuolated. Numerous processes of myocytes (P) and basement membrane-like material are also demonstrable here. Hypertrophied smooth muscle cell of a bizarre shape (lVI). Parts of endothelial cells (E). x 5,000.
Exp. Path. 27 (1985) 4
197
Results 1. Normotensive Wistar rats: Usually small arterioles or metarterioles were observed in the sections of the carotid bodies. Only one layer of smooth muscle cells enveloped the metarterioles incompletely. In one carotid body a bigger arteriole was studied more closely. The wall consisted of three loosely arranged layers of smooth muscle cells enveloped by a basal lamina. In the myocytes numerous pinocytic vesicles were present on the cell membrane and sometimes an increase in the density of the myofilaments was observed. An internal elastic lamina was partly present in the subendothelial space. The endothelial cells were situated on a basal lamina and connected by junctional complexes. The adventitia contained collagen bundles and single small processes of fibrocytes. 2. Spontaneously hypertensive rats (SHR): The wall of the big arterioles showed an extensive pad-like thickening (figs. 1 a, b). The smooth muscle cells of the media were hypertrophied, bizarre and with numerous projections (fig. 1). Many myocytes exhibited a marked increase in cell organelles. Mitochondria and rough endoplasmic reticulum were enlarged (fig. 1 a) and the Golgi apparatus was increased, too (fig. 2 b). The smooth muscle cells were partly surrounded by a basal lamina which was often detached from the cells. In the extracellular space numerous small processes of myocytes were demonstrable (figs. 1 b, 2 a). The extracellular space was extensively enlarged and partly vacuolated. It contained a thin, filament- and basement membrane-like material which was in connection with the basal lamina of the myocytes (figs. 1, 2 a). Moreover, there were partly hyperplastic endothelial cells (fig. 2 a) which were connected by junctional complexes. In the subendothelial space a multiplication of the basal laminae was visible, often of a whirl-like shape (fig. 2). There were no gaps in the endothelium. An internal elastic lamina could not be demonstrated.
Discussion Our ultrastructural findings of the arterioles within the carotid bodies of normotensive rats are identical with those of other authors (4, 18). Arterioles and metarterioles of other organs show a similar structure (5, 25, 26). In previous light-microscopic studies we found a pad-like thickening of the arteriolar wall within the glomus caroticum of SHR older than 5 weeks (7, 8). These pad-like areas show extensive alterations of the media in the study presented here. We found that hypertrophied myocytes exhibit an increased content of organelles and develop numerous irregular processes. Within this study we could not prove, however, that this is a true proliferation of the smooth muscle cells themselves. Apparently the enlargement of the media is caused by an extension of the extracellular space between the myocytes. The extracellular space seems to be transparent and contains thin, filamentand basement membrane-like substances. In previous light-microscopic observations we found a high amount of acid mucopolysaccharides in these pad-like areas of the intraglomic arterioles (8). It is well known that mucopolysaccharides are dissolved to a large extent by fixation techniques. Therefore, the vacuolisation of the extracellular space may be due to the dissolved acid mucopolysaccharides. The production of acid mucopolysaccharides by myocytes is well known (10, 14). In several forms of hypertension an increased content of acid mucopolysaccharides is observed in the media (9, 16, 17). The described alterations of the media of arterioles within the carotid bodies of SHR are of the same nature as the findings on arterioles in other organs caused by experimental hypertension (1,2,6, 15, 27, 28). Separation of the subendothelial space and multiplication of basement membrane-like material (1, 3, 13) also occurred in this area. At present one can only speculate about the functional effects of the vascular changes narrowing the lumina to a different extent. A reduced blood flow and/or a disturbed flow distribution in or through the glomus caroticum might be one result. A stimulation of the chemoreceptive tissue by ischemic hypoxia is therefore possible. On the other hand the blood
198
Exp. Path. 27 (1985) 4
vessels of the carotid bodies are innervated by sympathetic and parasympathetic nerves (19). The distribution of these perivascular nerves makes it possible that both autonomic inputs are capable of modifying carotid body blood flow (21, 22). The wall of the intraglomic arterioles [first or second order branches of the carotid body artery (18)] is strongly altered in SHR in the established phase of hypertension. A different reaction of these vessels on nervous stimulation followed by a disturbance of the vascular autoregulation of the carotid body is also imaginable. Several functional studies showed a varied function of the peripheral arterial chemoreceptors in SHR in the established phase of hypertension (11,12,23,24). The findings on the vascular system of the carotid bodies of SHR which are presented in this study might be one cause. But there are also some other possibilities for the interpretation of these phenomena (11, 12).
Acknowledgement We wish to thank Mrs. G. ENTER for her help in the preparation of the English text.
Literature 1. AMANO, S., and F. HAZAMA, Electron microscopic study of vascular changes in SHR. Jap. Heart J. 16, 299-301 (1975). 2. BACKWINKEL, K. P., H. THEMANN, G. SCHMITT und W. H. HAUSS, Elektronenmikroskopische
Untersuchungen fiber das Verhalten der glatten Muskelzellen in der Arterienwand. Virchows Arch. A 359,171-184 (1973). 3. BECKER, C. H., D. MATTIIIAS, E. ENGLER, H. J. HERRMANN, K. HECHT und CH. KREHER, Ultrastrukturelle Befunde an der Lamina elastica interna und ihrer Umgebung in Arteriolen von Ratten mit verschiedenen experimentellen Hypertonieformen. Exp. Path. 10, 40-56
(1974). 4. BOCK, P., Das Glomus caroticum der Maus. Springer Verlag, Berlin-Gottingen-New York 1973.
5. CAESAH, R., Gefii.Be und Herz im elektronenmikroskopischen Bild. In: M. STAEMMLER, Lehrbuch der speziellen pathologischen Anatomie. Erganzungsband 1. 1. Hii.lfte. De Gruyter, Berlin 1969. 6. GREDITZER, H. G., and V. W. FISCHER, A sequential ultrastructural study of different arteries in the hypertensive rat. Exp. Mol. Pathol. 29, 12-28 (1978). 7. HABECK, .J.-O., A. HONIG, C. PFEIFFER and M. SCHMIDT, The carotid bodies in spontaneously hypertensive (SHR) and normotensive rats. - A study concerning size, location and blood supply. Anat. Anz. 150, 374-384 (1981). 8. - CH. HUCKSTORF, and A. HONIG, Influence of age on the carotid bodies of spontaneously hypertensive (SHR) and normotensive rats. - II. Alterations of the vascular wall. Exp. Path. 27,
79-89 (1985).
9. HADJIISKY, P., and N. PEYRI, Hypertensive arterial disease and atherogenesis. Part. 1. Intimal changes in the o\~ spontaneously hypertensive rat (SHR). Atherosclerosis 44, 181-199 (1982). 10. HAUSS, W. H., Uber die Rolle des l\fesenchyms in der Genese der Arteriosklerose. Virchows Arch. A 359, 135-156 (1973). 11. HONIG, A., J.-O. HABECK, C. PFEIFFEH, M. SCHMIDT, C. HUCKSTORF, H. ROTTER and P. ECKERMANN, The carotid bodies of spontaneously hypertensive rats (SHR): A functional and morphologic study. Acta bioI. med. germ. 40, 1021-1030 (1981). 12. - Role of the arterial ehemoreeeptors in the reflex control of renal function and body fluid volumes in acute arterial hypoxia. In: H. ACKER and R. G. O'REGAN (eds.): Physiology of the Peripheral Arterial Chemoreceptors; chapter 14. Elsevier Biomedical Press!N orth- Holland, Amsterdam 1983, pp. 395-429. 13. HORI, S., T. NISHIDA, Y.MUIL\I, :VI. POMEROY and N. MUKAI, Ultrastructural studies on choroidal vessels in streptozotocin-diabetic and spontaneously hypertensive rats. Res. Comm. Chern. Pathol. Pharm. 29, 211-228 (1980). 14. JURUKO\VA, Z., und H. P. ROIIR, Beitrag zur Bildung bindegewebiger Matrix in glatten Muskelzellen. Pathol. europ. 3, .551--570 (1968). 15. KEHENYI, T., and I. HUTTNEH, Morphological changes of small muscular-type vessels and arterioles under the influence of various injuries. In: H. JELLINEK (Ed.): Arterial Lesions and Arteriosclerosis. Akademiai Kiado, Budapest 1974. 16. KUNZ, J., Pathologie der Arterienwand. VEB Verlag Yolk und Gesundheit, Berlin 1975. 17. MATTHIAS, D., V. MOHlTZ, E. ENGLER und C. H. BECKER, Histomorphologische GefaB- und Organbefunde und deren Abhiingigkeit vom Alter bei spontan hypertonen Ratten einer Linie des OKAMOTO-AOKI-Stammes. Dt. Gesundh.wesen 35, 1630-1638 (1980). 18. McDONALD, D. M., and D. T. LARUE, The ultrastructure and connections of blood vessels supplying the rat carotid body and carotid sinus. J. Neurocytol. 12, 117-153 (1983). Exp. Path. 27( 1985) 4
199
19. Me DONALD, D. M., A morphometric analysis of blood vessels and perivascular nerves in the rat carotid body. J. Neurocytol. 12, 155-199 (1983). 20. OKAMOTO, K., and K. AOKI, Development of a strain of spontaneously hypertensive rats. Japan. Circul. J. 27, 282-293 (1963).
21. O'REGAN, R. G., Control of carotid body chemoreceptors by autonomic nerves. Irish J. Med. Sci.
146, 199-205 (1977).
22. 23. 24. 25. 26. 27. 28.
Responses of carotid body chemosensory activity and blood flow to stimulation of sympathetic nerves in the cat. J. Physiol. 315, 81-98 (1981). PRZYBYLSKI, J., and W. BROZYNA, Reduced blood pressure response to carotid body chemoreceptor stimulation in spontaneously hypertensive rats. Acta Physiol. Pol. 32, 117-120 (1981). - A. TRZEBSKI, T. CZYZEWSKI, and J. J ODKOWSKI, Responses to hyperoxia, hypoxia, hypercapnia and almitrine in spontaneously hypertensive rats. Bull. europ. Physiopath. resp. 18 (Suppl. 4), 145-154 (1982). REALE, E., und H. RusKA, Die Feinstruktur der GefaBwande. Angiologica 2, 314-366 (1965). ROGGENDORF, W., and J. CERvos-NAVARRO, Ultrastructure of arterioles in the cat brain. Cell Tiss. Res. 178, 495-515 (1977). SPIRO, D., R. G. LATTES and J. WIEXER, The cellular pathology of experimental hypertension. I. Hyperplastic arteriolar-sclerosis. Amer. J. Path. 47, 19-49 (1965). TAKEBAYASHI, S., Ultrastructural studies on arteriolar lesions in experimental hypertension. J. Electron. Microsc. 19, 17-31 (1970).
200
Exp. Path. 27 (1985) 4