The pathogenesis of malignant hypertension is still unknown but the blood vessels are affected in virtually all forms of renal diseases. However, here we are concerned with the renal disorders which primarily affect the blood vessels. These are benign nephrosclerosis, malignant nephrosclerosis, senile arteriosclerotic kidney, mal infarction and acute cortical necrosis.
For the Consideration of nephrosclerosis it is necessary to remember that hypertension is divided into two large categories; that of unknown etiology, termed primary hypertension and comprising about 90% of all cases and that involving a known underlying pathologic process, termed secondary hypertension.
Secondary hypertension mar result from a host of diseases. Most important are renal disorders. Goldblatt et al. (1934) observed that these renal disorders lead to significant renal ischemia and this result has been confirmed by Holze(1951), Folkow(1657), Jackson(1958) and Conway(1960).
The literatures mention other factors, such as anoxia, toxic and allergic influences and possibly humoral agents which mar contribute to this form of vascular diseases (kincaid 1958, McMichael 1961).
Some recent observations on the Presence of antivascular antibodies in man and rat have suggested that an immune derangement contributes to the pathogenesis of the lesion (Koroskenyi et al., 1961; White and Grollman, 1963; Parionetto 1965).
The present investigation is aimed to study the lesions in the renal arterioles of rats induced by repeated injections of homologous kidney tissue with adjuvant as observed with the light, the fluorescent and the electron microscope in order to
contribute to the understanding of the immune processes in malignant hypertension.
Materials and Methods
Male and female albino rats, weighing around 200 gm, were divided into Group Ⅰ, Ⅱ, and Ⅲ. Group Ⅰ is a normal control and Group Ⅱ is an adjuvant control group. Group Ⅲ is a homologous kidney tissue and adjuvant injected group, that was
subdivided into 5 groups at various intervals. Eight injections of kidney tissue were given intraperitoneally once every other week in a dose of 0.5 ml of 30% fresh kidney tissue in an adjuvant mixture.
Necropsy specimens were obtained from kidneys and other organs from each groups of animals. Formalin-fixed paraffin sections were stained with hematoxylin and eosin, with Ⅴ an Gieson stain, with periodic acid-Schiff (PAS) and with Gomori's elastic stain.
Tissue blocks were also quickly frozen in dry ice-isopentane and stored at -20℃.
These were used for the fixation and staining of sections and for the Preparation of fluorescein labeled antisera. The antisera were also conjugated with fluorescein isothiocyanate (Nutritional Biochemical Co. U. S. A. made).
Some tissue blocks acre fixed in 1% osmium tetraoxide in veronal buffer at pH 7.4 for 2 hours each, and were dehydrated at 4℃ in a graded series of ethanol solution and embedded in Epon 812, and ultrathin sections were made with glass knife in 400
to 500 Å and were stained with saturated uranyl acetate. And the sections were examined in Hitachi HU 11-E electron microscope.
Results and Discussion
Blood pressure of group I is in average 97.2±5.2 mmHg., of group Ⅱ is 97.3±5.3 mmHg., ant of Group Ⅲ is up to 153.3±0.7 mmHg. The BUN (blood urea nitrogen) in group Ⅰ is 25.299, in group Ⅱ, 26.374 and 34.006 in group Ⅲ.
The blood pressure and BUN of group Ⅲ is higher than group Ⅰ and Ⅱ. The proteinuria was also more intensive in group Ⅲ than in other groups.
The antikidney antisera were detected in all animals of group Ⅲ as 1:640 dilution. Albumin to globulin ratio was reversed in group Ⅲ. At necropsy, the kidney and other organs showed no abnormalities in group Ⅰ and Ⅱ, but group Ⅲ showed fecal ischemia and petechia on the kidney surface without inflammatory
reaction while ocher organs showed no gross abnormalities.
Histologically, the group Ⅲ animals showed intimal fibrosis, Patch-formation, and atheroma plaque on the intima of arterioles. The internal and external elastic lamella were duplicated or necrotic. The atheroma plaque narrowed or obliterated the arterial lumens.
Hyaline degeneration, proliferation of fibroblasts and degeneration or edema of smooth muscle cells were shown in the media.
The glomeruli had nephrosclerotic changes, the proximal renal tubules showed many hyaline or waxy easts.
The deposition of plasma protein hart been investigated with immunofluorescent techniques in group Ⅲ animals.
Anti-kidney anti-sera were identified in the arterioles and hyaline necrosis in the glomerular lesions of group Ⅲ.
Electron microscopic findings showed swelling of mitochondria, Golgi dilatation and the changes of endoplasmic reticulum, and lysosomal vacuoles in the cytoplasm.
The pinocytotic vesicles were observed near the basement membrane of endoth디ial cells of renal arterioles. The elastic reduplication or necrosis with hyaline deposition were observed in the media of arterioles. These findings were mon prominent in group Ⅲ animals.
The deposition of anti-kidney anti-sera has been investigated with immunofluorescent techniques in homologous kidney tissue injected animals of group Ⅲ, as a renal hypertension. These findings acre identified in talc renal arteriolar hyaline necrosis and in the glomerular lesions.
Thc hyperplastic proliferation of the intima of renal arteries were devoid of the anti-sera investigated.
The marked duplication of internal elastic lamella and necrosis were identified in the intraparencbymal renal arteries.
The hypothesis of the present study is that one of the mechanisms of tissue damage in renal arterioles or arteries is talc deposition or formation of immune complex in an area of minimal alterations with subsequent fixation of complement,
ensuing damage and increased permeability of all plasma proteins.