(Stroke. 1999;30:695-696.)
© 1999 American Heart Association, Inc.
Letters to the Editor |
Spontaneous Stroke in Renovascular Hypertensive Rats
The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
To the Editor:
Zeng and colleagues1 recently published a potentially important study on the spontaneous stroke in 2-kidney, 2-clip renovascular hypertensive rats. Blood pressure rose to an average of 225 mm Hg 6 weeks postoperatively. Animals displaying neurological symptoms were killed on the third day, and those surviving without neurological symptoms were killed at postoperative week 40. Stroke occurred in 34, including 7 hematomas in 55 animals (61.8%). Microscopic examination revealed fibrinoid necrosis, hyaline degeneration, and hyperplasia of the walls of arterioles and small arteries with or without cell proliferation in the brain. These vascular lesions were not observed in the hypertensive animals without gross brain lesions. I read this paper with great interest, because we published a paper on the cerebral hemorrhage in renovascular hypertensive rabbits over 30 years ago.2 Despite the species difference, there are many similarities between the 2 studies. I would like to compare the recent study by Zeng and colleagues with our old one and offer some comments.
In our old study,2 we made rabbits hypertensive by the 2-kidney, 2-clip or 1-kidney, 1-clip procedure. The 2-kidney, 2-clip group was divided into one with moderate narrowing of the renal arteries and the other with a lesser degree of narrowing of the renal arteries. All animals that spontaneously died were autopsied for gross and microscopic examination. Most of the deaths occured within 50 days after renal artery constriction. Animals surviving for a long term were not included in this study. Spontaneous cerebral hemorrhages were found in 31 of a total of 74 spontaneously dead animals (41.9%). There were no significant differences in the incidence of cerebral hemorrhage among the 3 groups. Gross hemorrhages of other organs, including stomach and intestine, were also frequently observed in animals both with and without cerebral hemorrhage. The gross observations indicated that the cerebral hemorrhage developed on the basis of generalized hemorrhagic disorders. Indeed, we later observed prolongation of the clotting time in some of renovascular hypertensive rabbits,3 and Wiener and colleagues4 showed evidence for the increased vascular permeability in renovascular hypertensive rabbits. Microscopic examination showed fibrinoid necrosis of arterioles and small arteries of the brain in almost all animals with cerebral hemorrhage and in about half of the animals without cerebral hemorrhage. Also, the vascular lesions were frequently found in the stomach, intestines, and other organs of both animals with or without cerebral hemorrhage. There were dilated small arteries with fibrinoid necrosis in the vicinities of hemorrhagic foci in the brain, giving the appearance of a pseudoaneurysm. Miliary aneurysms of the iris and brain associated with a high risk of cerebral hemorrhage in renal hypertensive rabbits were reported by Santos-Buch and colleagues about 20 years ago.5
As in the old and recent studies described, the simple procedure of renal artery constriction was followed by a persistent rise of blood pressure high enough to induce stroke. Both studies indicated that fibrinoid necrosis and related lesions of arterioles and small arteries were the vascular lesions responsible for cerebral hemorrhage. In our study, the vascular lesions were not localized in the brain but instead widely distributed in other organs. Although our article did not refer to the matter, I believe that the generalized vascular lesions were vascular manifestations of the malignant hypertension and the cerebral hemorrhage accompanied by multiple visceral hemorrhages resulted from malignant transformation of renovascular hypertension. It remains unclear whether the renovascular hypertension in rats developed by Zeng and colleagues1 was malignant or not, because their study lacked gross and microscopic examination of organs other than the brain. It may be malignant, because the microphotographs of cerebral arteries illustrated in the article closely resemble those illustrated in our paper, and they appear to be more fulminant than vascular lesions observed in the human brain with hypertensive hemorrhage.
References
1.
Zeng J, Zhang Y, Mo J, Su Z, Huang R. Two-kidney,
two clip renovascular hypertensive rats can be used as stroke-prone
rats. Stroke. 1998;29:1708–1714.
2. Ikeda M, Fujii J, Terasawa F, Hosoda S, Kurihara H, Kimata S. Cerebral hemorrhage in experimental renal hypertension. Jpn Heart J. 1964;5:466–473.
3. Fujii J, Hosoda S, Kurihara H, Kimata S, Ikeda M. Blutgerinnungsstörung bei Kaninchen mit der Nierenarteriendrosserung. Klin Wochenschr. 1967;45:794–795.
4. Wiener J, Lattes RG, Meltzer BG, Spiro D. The cellular pathology of experimental hypertension, IV: evidence for increased vascular permeability. Am J Pathol. 1969;54:187–207.[Medline] [Order article via Infotrieve]
5.
Santos-Buch CA, Goodhue WW, Ewald BH. Concurrence of
iris aneurysms and cerebral hemorrhage in hypertensive
rabbits. Arch Neurol. 1976;33:96–103.
Response
Department of Neurology
Department of Neurophthalmology, Ophthalmic Center
Department of Neurology, First Affiliated Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou, People's Republic of China
Key Words: hypertension • rats
We appreciate the interest of Dr Fujii in our article describing spontaneous stroke in renovascular hypertensive rats.1 In our study, the systolic blood pressure reached a peak mean value of 215±23 mm Hg at 172±48 days postoperatively in 2-kidney, 2 clip renovascular hypertensive rats (2k2c RHR). Thirty-four of 55 2k2c RHR showed brain lesions including cerebral infarction, hemorrhage, both cerebral infarction and hemorrhage, and subarachnoid hemorrhage after 6 weeks postoperatively, in which the onset time of cerebral hemorrhage was 98±31 days postoperatively in the rats. Similar cerebral hemorrhage was also found in the renovascular hypertensive rabbits in the old study of Ikeda and colleagues.2 Except for the species difference, the main lesion of brain was cerebral hemorrhage that developed on the basis of generalized hemorrhage disorders and occurred within 50 days after renal artery constriction in the rabbits. This kind of brain lesion in the rabbits was more similar to that in 1-kidney, 1-clip renovascular hypertensive rats than that in 2-kidney, 2-clip ones in our study.1
Multiple visceral hemorrhages were not often seen in the 2k2c RHR when they were perfused and killed for histological examination, although the study lacked in gross and microscopic examination of organs other than the brain. But in the other study,3 we found that small coronary arteries in all of the 2k2c RHR displayed medial thickness and cell proliferation of the wall or stenotic lumen without fibrinoid necrosis or atherosclerosis. Multiple myocardial necroses were found in 23 of 55 2k2c RHR. We agree with Dr Fujii that hypertension in some of the 2k2c RHR may be malignant, since the main lesion of cerebral artery in the rats that experienced stroke within 10 weeks after renal artery constriction was fibrinoid necrosis.1 The 2k2c RHR displayed cerebral lesions similar to those found in stroke-prone spontaneously hypertensive rats developed by Okamota and colleagues,4 and some investigators have considered the stroke-prone spontaneously hypertensive rats as experimental models of malignant hypertension.5
References
1. Zeng J, Zhang Y, Mo J, Su Z, Huang R. Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats. Stroke. 1998;29:1708–1714.
2. Ikeda M, Fujii J, Terasawa F, Hosoda S, Kurihara H, Kimata S. Cerebral hemorrhage in experimental renal hypertension. Jpn Heart J. 1964;5:466–473.
3. Zeng J, Huang R. Cardiac lesions in stroke-prone renovascular hypertensive rats. Chin J Hypertens. 1995;3:18–20.
4. Okamota K, Yamoyi Y, Nagaoka. Establishment of the stroke-prone sponeously hypertensive rats (RHR). Circ Res. 1974;34–35(suppl 1):143–153.
5. Ogata J, Fujishima M, Tamaki K, Nagatomi Y, Ishitsuka T, Omae T. Stroke-prone spontaneously hypertensive rats as experimental model of malignant hypertension, I: a light- and electron-microscopic study of the brain. Acta Neuropathol (Berl). 1980;51:179–184.[Medline] [Order article via Infotrieve]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||