‘Spontaneous’ intimal loss in arteries of old hypertensive rats and the experimental production of similar lesions in young rabbits

Mtcron. 1980,Vol.: I I, pp.457458

PergamonPressLid. Printedin GreatBritain

'SPONTANEOUS' INTIMAL LOSS IN ARTERIES OF OLD HYPERTENSIVE RATS AND THE EXPERIMENTAL PRODUCTION OF SIMILAR LESIONS IN YOUNG RABBITS*

G. R. CAMPBELL Department of Anatomy, University of Melbourne, Parkville 3052, Australia

J. H. CAMPBELL Baker Medical Research Institute, Commercial Road, Prahran 3181, Australia Renal arteries of 4-18 month Kyoto-Wistar spontaneously hypertensive and normotensive virgin male rats have been examined. Numerous regions where the internal elastic lamina (IEL) was absent over all or part of the vessel circumference for distances of up to 1,000 ~m were observed (Fig. I). In the majority of cases there was no sign of degeneration or fragmentation of the IEL and the site of rupture appeared as a clean abrupt break (Fig. 2 ) The endothelial cells overlying such areas were usually large and contained substantial amounts of endoplasmlc reticulum, mitochondria and Golgi. Areas where recent breaks in the IEL had occurred (as determined by endothelial cell mitosis) could be distinguished. Here the underlying media contained necrotic cells, synthetlc-state smooth muscle cells (i) and cells with a fibroblastic appearance (presumably derived from the blood or adventitia). Particularly noticeable in the spontaneously hypertensive rats were areas of intense smooth muscle cell proliferation, adjacent to the lesions. Here the smooth muscle cells were smaller than those of the media and were longitudinally placed with respect to the length of the vessel. Due to new elastln formation and a process of elastosis these areas of smooth muscle were either intlmal or medial in location. Similar breaks in the IEL of caudal arteries of Wistar rats have recently been described (2). Similar lesions to those described in renal arteries of rats have not been observed in 2-5 month normotenslve rabbits. However, rupture of the IEL and formation of a neo-intima of smooth muscle cells within the renal artery can be created by looping the vessel around a piece of polyethylene tubing in such a way as to avoid occlusion of blood flow. After two weeks the endothelial cells covering these areas were enlarged and separated from the underlying longitudinally orientated intlmal smooth muscle cells by a large extracellular space containing flocculent basal lamlna-like material. It was often difficult to distinguish Intima from media because the IEL was ruptured over lengths of up to 800 ~m (Fig. 3). The majority of cells within these areas were smooth muscle, often in a synthetic -state phenotype. These two models will provide further information on factors involved in rupture or fragmentation of elastic lamellae and related intimal hyperplasia, both of which have been implicated in the etiology of atherosclerosis.

REFERENCES i.

J. Chamley-Campbell, C.R. Campbell & R. Ross, The smooth muscle cell in culture, Physiological Reviews 59, I (1979).

2.

~. Osborne-Pellegrln, "Spontaneous" lesions in the intima in the rat caudal artery, Laboratory InvestlF, atlon 40, 668 (1979).

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! Fig. I Hypertensive rat renal artery. Note: Rupture of IEL

Rabbit renal artery

Fig. 2 TEM of similar area to Fig. I. Note: Ruptured area covered by endothellum and presence of flbroblastoid cells beneath.

Fl$. 3 2 weeks a f t e r b e i n g looped around p o l y e t h y l e n e t u b i n g . Note: Fragmented IEL and n e o i n t i m a .