A relation between hypertension, atherosclerosis, and stroke is well documented in humans. We report a similar relation in two hypertensive cynomolgus monkeys with severe cerebral atherosclerosis. In our primate model hypertension is induced by surgical coarctation of the aorta. These monkeys, when fed an atherogenic diet, develop severe cerebrovascular atherosclerosis. In this setting two monkeys developed spontaneous cerebral hemispheric strokes that occurred during treatment of hypertension. Since the strokes were topographically related to severe atherosclerotic narrowing of cerebral arteries and occurred without evidence of either thrombosis or embolization, they are presumed to be related to disturbances of blood flow. In both humans and animals cerebral perfusion is autoregulated to a constant flow over a wide range of mean arterial blood pressures. In hypertension both the upper and lower limits of autoregulation are increased. With treatment of hypertension readaptation to more normal levels is reported to be inconsistent and slow to develop. It is therefore postulated that the strokes in these two monkeys were due to hypoperfusion as a result of the combination of pharmacologic reduction in blood pressure and severe occlusive atherosclerosis. 4 reported severe cerebrovascular atherosclerosis when the monkeys were fed an atherogenic diet. We report two cases of spontaneous stroke in this monkey model of cerebrovascular atherosclerosis. These monkeys were part of a group of 16 similarly treated animals on a pharmacologic regimen to reduce elevated blood pressure. Within this group, these two monkeys showed severe cerebrovascular atherosclerosis and the most marked reduction in blood pressure, suggesting that antihypertensive medication played a role in their pathogenesis.
Materials and MethodsBoth brains were embedded whole in celloidin and cut in gapless serial sections at a thickness of 35 /im. Every twentieth section was stained with Nissl's stain for tissue reactions and vascular pathology, and the adjacent section was stained with Loyez stain for myelinated fibers. The large arteries at the base of the brain and the extracranial internal carotid arteries were removed at the time of autopsy and visually inspected at a magnification of 2 x for atherosclerotic plaques, thrombi, and emboli. Representative sections from predetermined sites (all areas labeled in Figure 4) and Received January 23, 1987; accepted August 3, 1987. all grossly visible atherosclerotic plaques were embedded in polyethylene glycol with 4-/u.m-thick sections stained with oil red O, Verhoeff-van Gieson's stain, and toluidine blue. Morphometric measurements were performed on the histologic cross sections with a Zeiss MOP III Image Analyzer (Thornwood, New York). Lesion size or intimal area was determined by digitizing the area between the internal elastic membrane and the luminal surface of the artery. The percent stenosis (shown in Figure 4) is the maximum narrowing observed in all arteries showing atherosclerosis and was calcul...